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Dr Mark Wood

Associate Professor in Organic Chemistry

3450

Geoffrey Pope 225

Geoffrey Pope Building, University of Exeter , Stocker Road, Exeter, EX4 4QD, UK

Overview

I am an organic chemist with research interests that cover a wide range of aspects of synthesis. Recent studies have focused on asymmetric synthesis of structurally complex amino acids, using what has proved to be a very versatile radical-based methodology and also the use of structurally unusual heterocycles for masking the reactivity of synthetically valuable functional groups. In this area, we have developed a methodology for the incorporation of protected isocyanates into organic molecules and this chemistry is being applied to the synthesis of a diverse set of biologically important, nitrogen-containing heterocycles. My teaching activities cover all aspects of organic chemistry from basic structure and bonding in organic molecules, to complex organic synthesis. I am a member of the Biological Chemistry research group.

Qualifications

1990 DPhil Organic Chemistry, University of Oxford
1989 MA Chemistry, Balliol College, University of Oxford
1986 BA (Hons) Chemistry, Balliol College, University of Oxford

Career

2022-present Associate Professor in Organic Chemistry, Biosciences, University of Exeter

2007-2022 Senior Lecturer in Organic Chemistry, Biosciences, University of Exeter

2005-2007 Lecturer in Organic Chemistry, Biosciences, University of Exeter
1996-2005 Lecturer in Organic Chemistry, School of Chemistry, University of Exeter
1990-1996 GlaxoWellcome (originally Glaxo) Fellow and Tutor in Organic Chemistry, St Catherine's College, University of Oxford)

Research group links

Cellular and Chemical Biology

Research

Research interests

The use of radical-based methodology in the synthesis of highly substituted amines and amino acids. The aim of these studies has been to develop a much-needed general synthetic route to amino acids (and other amine derivatives) possessing a quaternary chiral centre alpha-to the nitrogen atom and in particular, alpha,alpha-disubstituted alpha-amino acids. The central theme of this methodology is the formation of alpha-aminoalkyl radicals from existing amino acid and alpha-amino alcohol derivatives by 1,5-hydrogen atom transfer and the subsequent trapping of these radicals with appropriate radicalphiles, thus generating quaternary centres with high efficiency and excellent stereocontrol. This ongoing area of research has led to further investigations into the 1,5-hydrogen atom transfer process and in particular, studies into the effectiveness of deuterium as a protecting group for C-H bonds in radical and carbene chemistry.

Synthetic applications of structurally 'unusual' heterocycles. The second major area of my group's research has involved studies into the use of structurally "unusual" heterocycles as protected, reactive functional groups in organic synthesis. In particular, we have developed methods for the stereoselective incorporation of the 1,2,4-dithiazolidine-3,5-dione (Dts imide) moiety into molecules as a masked isocyanate equivalent. These studies have also revealed intriguing and unexpected physical properties associated with the parent imide heterocycle (particularly in terms of its acidity) and as a result, studies involving related heterocycles are proposed.

Investigation of photoinitiated Bergman cyclisation reactions using high-resolution laser spectroscopy. The importance of the Bergmann cyclisation reaction in the mode of action of anti-tumour enediyne antibiotics such as calicheamicin-alpha and the neocarzinostatins provided the starting point for this collaborative project for which Dr David Smith is the principal investigator. Whilst much has been written about this reaction, relatively little characterisation has been carried out on the reaction intermediates. My involvement in this project is from the synthetic angle, and I am currently directing and supervising the preparation of the required enediyne cyclisation precursors.

Research grants

2004 AstraZeneca
CASE Studentship � "New, Heterocyclic Routes to Protected Isocyanates and Ketenes"
2004 ESRC
"Investigation of Photoinitiated Bergman Cyclisation Reactions Using High-Resolution Laser Spectroscopy"
2004 Pfizer
"Synthesis of Amino Acids"
2003 ESRC
"Deuterium � A Remarkably Simple, Recyclable Protection Protocol in Radical and Carbene Chemistry"
2001 Celltech (subsequently UCB Group)
"A Versatile Methodology for the Preparation of Highly Substituted Amine Derivatives Including the Use of Deuterium as a Recyclable Protecting Group"

Publications

Key publications | Publications by category | Publications by year

Key publications

Fox B, Schantz J-T, Haigh R, Wood ME, Moore PK, Viner N, Spencer JPE, Winyard PG, Whiteman M (2012). Inducible hydrogen sulfide synthesis in chondrocytes and mesenchymal progenitor cells: is H2S a novel cytoprotective mediator in the inflamed joint?. J Cell Mol Med, 16(4), 896-910. Abstract. Author URL.

Perry MM, Hui CK, Whiteman M, Wood ME, Adcock I, Kirkham P, Michaeloudes C, Chung KF (2011). Hydrogen sulfide inhibits proliferation and release of IL-8 from human airway smooth muscle cells. Am J Respir Cell Mol Biol, 45(4), 746-752. Abstract. Author URL.

Yong Q-C, Cheong JL, Hua F, Deng L-W, Khoo YM, Lee H-S, Perry A, Wood M, Whiteman M, Bian J-S, et al (2011). Regulation of heart function by endogenous gaseous mediators-crosstalk between nitric oxide and hydrogen sulfide. Antioxidants & Redox Signaling, 14(11), 2081-2091.

Wood ME, Bissiriou S, Lowe C, Norrish AM, Sénéchal K, Windeatt KM, Coles SJ, Hursthouse MB (2010). Synthetic use of the primary kinetic isotope effect in hydrogen atom transfer: generation of α-aminoalkyl radicals. Org Biomol Chem, 8(20), 4653-4665. Abstract. Author URL.

Publications by category

Journal articles

Curnow A, Anayo L, Magnussen A, Perry A, Wood M (In Press). AN EXPERIMENTAL INVESTIGATION OF a NOVEL IRON CHELATING PROTOPORPHYRIN IX PRODRUG FOR THE ENHANCEMENT OF PHOTODYNAMIC THERAPY. Lasers in Surgery and Medicine

Wood ME, Alexander BE, Coles SJ, Fox BC, Khan TF, Maliszewski J, Perry A, Pitak MB, Whiteman M (In Press). investigating the generation of hydrogen sulfide from the phosphonamidodithioate slow-release donor GYY4137. MedChemComm

Lohakul J, Jeayeng S, Chaiprasongsuk A, Torregrossa R, Wood ME, Saelim M, Thangboonjit W, Whiteman M, Panich U (2022). Mitochondria-Targeted Hydrogen Sulfide Delivery Molecules Protect Against UVA-Induced Photoaging in Human Dermal Fibroblasts, and in Mouse Skin in Vivo. Antioxid Redox Signal, 36(16-18), 1268-1288. Abstract. Author URL.

da Costa Marques LA, Teixeira SA, de Jesus FN, Wood ME, Torregrossa R, Whiteman M, Costa SKP, Muscará MN (2022). Vasorelaxant Activity of AP39, a Mitochondria-Targeted H2S Donor, on Mouse Mesenteric Artery Rings in Vitro. Biomolecules, 12(2). Abstract.

Curnow A, Magnussen A, Reburn C, Perry A, Wood M (2021). Experimental investigation of a combinational iron chelating. protoporphyrin IX prodrug for fluorescence detection and photodynamic therapy. Lasers in Medical Science

Allen CL, Wolanska K, Malhi NK, Benest AV, Wood ME, Amoaku W, Torregrossa R, Whiteman M, Bates DO, Whatmore JL, et al (2021). Hydrogen Sulfide is a Novel Protector of the Retinal Glycocalyx and Endothelial Permeability Barrier. Frontiers in Cell and Developmental Biology, 9 Abstract.

Steinberg G, Schuster M, Gurr SJ, Schrader TA, Schrader M, Wood M, Early A, Kilaru S (2020). A lipophilic cation protects crops against fungal pathogens by multiple modes of action. Nat Commun, 11(1). Abstract. Author URL.

Hansbro NG, Pacitti D, Brown A, Torregrossa R, Balachandran L, Kumar V, Wood M, Haw T-J, Scotton C, Whiteman M, et al (2020). Mitochondria-targeted Sulfide Delivery Molecules – New and Novel Players that can Suppress and Reverse Cigarette Smoke-induced Inflammasome Activity. The Journal of Immunology, 204(1_Supplement), 68.9-68.9.

Curnow A, Perry A, Wood M (2019). Improving in vitro photodynamic therapy through the development of a novel iron chelating aminolaevulinic acid prodrug. Photodiagnosis Photodyn Ther, 25, 157-165. Abstract. Author URL.

Williams E, Whiteman M, Wood ME, Wilson ID, Ladomery MR, Allainguillaume J, Teklic T, Lisjak M, Hancock JT (2019). Investigating ROS, RNS, and H2S-Sensitive Signaling Proteins. Methods Mol Biol, 1990, 27-42. Abstract. Author URL.

Stevens M, Payne M, Innes E, Torregrossa RO, Wood M, Stevens MKO, Whiteman MO, Oltean SO (2018). A novel mitochondria‐targeted hydrogen sulfide delivery molecule prevents uraemia and diabetes‐induced renal cell oxidative stress. The FASEB Journal, 32(S1), 619.10-619.10.

Brown AR, Green J, Moreman J, Gunnarsson L, Mourabit S, Ball J, Winter M, Trznadel M, Correia A, Hacker C, et al (2018). Cardiovascular Effects and Molecular Mechanisms of Bisphenol a and its Metabolite MBP in Zebrafish. Environmental Science and Technology

Moreman J, Takesono A, Trznadel M, Winter MJ, Perry A, Wood ME, Rogers NJ, Kudoh T, Tyler CR (2018). Estrogenic Mechanisms and Cardiac Responses Following Early Life Exposure to Bisphenol a (BPA) and its Metabolite 4-Methyl-2,4-bis( p-hydroxyphenyl)pent-1-ene (MBP) in Zebrafish. Environ Sci Technol, 52(11), 6656-6665. Abstract. Author URL.

Potor L, Nagy P, Méhes G, Hendrik Z, Jeney V, Pethó D, Vasas A, Pálinkás Z, Balogh E, Gyetvai Á, et al (2018). Hydrogen Sulfide Abrogates Hemoglobin-Lipid Interaction in Atherosclerotic Lesion. Oxidative Medicine and Cellular Longevity, 2018 Abstract.

Latorre E, Torregrossa R, Wood ME, Whiteman M, Harries LW (2018). Mitochondria-targeted hydrogen sulfide attenuates endothelial senescence by selective induction of splicing factors HNRNPD and SRSF2. Aging (Albany NY), 10(7), 1666-1681. Abstract. Author URL.

Cao X, Xiong S, Zhou Y, Wu Z, Ding L, Zhu Y, Wood ME, Whiteman M, Moore PK, Bian J-S, et al (2018). Renal Protective Effect of Hydrogen Sulfide in Cisplatin-Induced Nephrotoxicity. Antioxid Redox Signal, 29(5), 455-470. Abstract. Author URL.

Karwi QG, Bornbaum J, Boengler K, Torregrossa R, Whiteman M, Wood ME, Schulz R, Baxter GF (2017). AP39, a mitochondria-targeting hydrogen sulfide (H2 S) donor, protects against myocardial reperfusion injury independently of salvage kinase signalling. Br J Pharmacol, 174(4), 287-301. Abstract. Author URL.

Lobb I, Jiang J, Lian D, Liu W, Haig A, Saha MN, Torregrossa R, Wood ME, Whiteman M, Sener A, et al (2017). Hydrogen Sulfide Protects Renal Grafts Against Prolonged Cold Ischemia-Reperfusion Injury via Specific Mitochondrial Actions. Am J Transplant, 17(2), 341-352. Abstract. Author URL.

Neale H, Deshappriya N, Arnold D, Wood ME, Whiteman M, Hancock JT (2017). Hydrogen sulfide causes excision of a genomic island in Pseudomonas syringae pv. phaseolicola. European Journal of Plant Pathology, 149(4), 911-921. Abstract.

Nußbaum BL, Vogt J, Wachter U, McCook O, Wepler M, Matallo J, Calzia E, Gröger M, Georgieff M, Wood ME, et al (2017). Metabolic, Cardiac, and Renal Effects of the Slow Hydrogen Sulfide-Releasing Molecule GYY4137 During Resuscitated Septic Shock in Swine with Pre-Existing Coronary Artery Disease. Shock, 48(2), 175-184. Abstract. Author URL.

Rodrigues L, Ekundi-Valentim E, Florenzano J, Cerqueira ARA, Soares AG, Schmidt TP, Santos KT, Teixeira SA, Ribela MTCP, Rodrigues SF, et al (2017). Protective effects of exogenous and endogenous hydrogen sulfide in mast cell-mediated pruritus and cutaneous acute inflammation in mice. Pharmacol Res, 115, 255-266. Abstract. Author URL.

Ahmad A, Olah G, Szczesny B, Wood ME, Whiteman M, Szabo C (2016). AP39, a mitochondrially targeted hydrogen sulfide donor, exerts protective effects in renal epithelial cells subjected to oxidative stress in vitro and in acute renal injury in vivo. Shock, 45(1), 88-97.

This study evaluated the effects of AP39 [(10-oxo-10-(4-(3-Thioxo-3H-1,2-dithiol-5yl) phenoxy)decyl) triphenyl phosphonium bromide], a mitochondrially targeted donor of hydrogen sulfide (H2S) in an in vitro model of hypoxia/oxidative stress injury in NRK-49F rat kidney epithelial cells (NRK cells) and in a rat model of renal ischemia-reperfusion injury. Renal oxidative stresswas induced by the addition of glucose oxidase, which generates hydrogen peroxide in the culture medium at a constant rate. Glucose oxidase (GOx)-induced oxidative stress led to mitochondrial dysfunction, decreased intracellular ATP content, and, at higher concentrations, increased intracellular oxidant formation (estimated by the fluorescent probe 2, 7-dichlorofluorescein, DCF) and promoted necrosis (estimated by the measurement of lactate dehydrogenase release into the medium) of the NRK cells in vitro. Pretreatment with AP39 (30-300 nM) exerted a concentration-dependent protective effect against all of the above effects of GOx. Most of the effects of AP39 followed a bell-shaped concentration-response curve; at the highest concentration of GOx tested, AP39 was no longer able to afford cytoprotective effects. Rats subjected to renal ischemia/reperfusion responded with a marked increase (over four-fold over sham control baseline) blood urea nitrogen and creatinine levels in blood, indicative of significant renal damage. This was associated with increased neutrophil infiltration into the kidneys (assessed by the myeloperoxidase assay in kidney homogenates), increased oxidative stress (assessed by the malondialdehyde assay in kidney homogenates), and an increase in plasma levels of IL-12. Pretreatment with AP39 (0.1, 0.2, and 0.3 mg/kg) provided a dose-dependent protection against these pathophysiological alterations; the most pronounced protective effect was observed at the 0.3 mg/kg dose of the H2S donor; nevertheless, AP39 failed to achieve a complete normalization of any of the injury markers measured. The partial protective effects of AP39 correlated with a partial improvement of kidney histological scores and reduced TUNEL staining (an indicator of DNA damage and apoptosis). In summary, the mitochondria-Targeted H2S donor AP39 exerted dose-dependent protective effects against renal epithelial cell injury in vitro and renal ischemia-reperfusion injury in vivo. We hypothesize that the beneficial actions of AP39 are related to the reduction of cellular oxidative stress, and subsequent attenuation of various positive feed-forward cycles of inflammatory and oxidative processes.

Abstract.

Wood ME, Chatzianastasiou A, Bibli S-I, Andreadou I, Efentakis P, Kaludercic N, Whiteman M, Di Lisa F, Daiber A, Manolopoulos VG, et al (2016). Cardioprotection by H2S donors: nitric oxide-dependent and -independent mechanisms. Journal of Pharmacology and Experimental Therapeutics

Lin S, Visram F, Liu W, Haig A, Jiang J, Mok A, Lian D, Wood ME, Torregrossa R, Whiteman M, et al (2016). GYY4137, a Slow-Releasing Hydrogen Sulfide Donor, Ameliorates Renal Damage Associated with Chronic Obstructive Uropathy. J Urol, 196(6), 1778-1787. Abstract. Author URL.

Coavoy-Sánchez SA, Rodrigues L, Teixeira SA, Soares AG, Torregrossa R, Wood ME, Whiteman M, Costa SKP, Muscará MN (2016). Hydrogen sulfide donors alleviate itch secondary to the activation of type-2 protease activated receptors (PAR-2) in mice. Pharmacol Res, 113(Pt A), 686-694.

Hydrogen sulfide (H2S) has been highlighted as an endogenous signaling molecule and we have previously found that it can inhibit histamine-mediated itching. Pruritus is the most common symptom of cutaneous diseases and anti-histamines are the usual treatment; however, anti-histamine-resistant pruritus is common in some clinical settings. In this way, the involvement of mediators other than histamine in the context of pruritus requires new therapeutic targets. Considering that the activation of proteinase-activated receptor 2 (PAR-2) is involved in pruritus both in rodents and humans, in this study we investigated the effect of H2S donors on the acute scratching behavior mediated by PAR-2 activation in mice, as well as some of the possible pharmacological mechanisms involved. The intradermal injection of the PAR-2 peptide agonist SLIGRL-NH2 (8-80nmol) caused a dose-dependent scratching that was unaffected by intraperitoneal pre-treatment with the histamine H1 antagonist pyrilamine (30mg/kg). Co-injection of SLIGRL-NH2 (40nmol) with either the slow-release H2S donor GYY4137 (1 and 3nmol) or the spontaneous donor NaHS (1 and 0.3nmol) significantly reduced pruritus. Co-treatment with the KATP channel blocker glibenclamide (200nmol) or the nitric oxide (NO) donor sodium nitroprusside (10nmol) abolished the antipruritic effects of NaHS; however, the specific soluble guanylyl cyclase inhibitor ODQ (30μg) had no significant effects. The transient receptor potential ankyrin type 1 (TRPA1) antagonist HC-030031 (20μg) significantly reduced SLIGRL-NH2-induced pruritus; however pruritus induced by the TRPA1 agonist AITC (1000nmol) was unaffected by NaHS. Based on these data, we conclude that pruritus secondary to PAR-2 activation can be reduced by H2S, which acts through KATP channel opening and involves NO in a cyclic guanosine monophosphate (cGMP)-independent manner. Furthermore, TRPA1 receptors mediate the pruritus induced by activation of PAR-2, but H2S does not interfere with this pathway. These results provide additional support for the development of new therapeutical alternatives, mainly intended for treatment of pruritus in patients unresponsive to anti-histamines.

Abstract. Author URL.

Wedmann R, Onderka C, Wei S, Szijártó IA, Miljkovic JL, Mitrovic A, Lange M, Savitsky S, Yadav PK, Torregrossa R, et al (2016). Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation. Chemical Science, 7(5), 3414-3426. Abstract.

Hedegaard ER, Gouliaev A, Winther AK, Arcanjo DDR, Aalling M, Renaltan NS, Wood ME, Whiteman M, Skovgaard N, Simonsen U, et al (2016). Involvement of Potassium Channels and Calcium-Independent Mechanisms in Hydrogen Sulfide-Induced Relaxation of Rat Mesenteric Small Arteries. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 356(1), 53-63. Author URL.

Lin S, Visram F, Lobb I, Liu W, Haig A, Jiang J, Mok A, Lian D, Wood ME, Whiteman M, et al (2016). MP58-18 EXOGENOUS HYDROGEN SULFIDE TREATMENT REDUCES RENAL FIBROSIS ASSOCIATED WITH CHRONIC URETERAL OBSTRUCTION BY ATTENUATING EPITHELIAL-MESENCHYMAL TRANSITION. Journal of Urology, 195(4S).

Karwi QG, Whiteman M, Wood ME, Torregrossa R, Baxter GF (2016). Pharmacological postconditioning against myocardial infarction with a slow-releasing hydrogen sulfide donor, GYY4137. Pharmacological Research, 111, 442-451.

Gerő D, Torregrossa R, Perry A, Waters A, Le-Trionnaire S, Whatmore JL, Wood M, Whiteman M (2016). The novel mitochondria-targeted hydrogen sulfide (H2S) donors AP123 and AP39 protect against hyperglycemic injury in microvascular endothelial cells in vitro. Pharmacol Res, 113(Pt A), 186-198. Abstract. Author URL.

Perry A, Green SJ, Horsell DW, Hornett SM, Wood ME (2015). A pyrene-appended spiropyran for selective photo-switchable binding of Zn(II): UV-visible and fluorescence spectroscopy studies of binding and non-covalent attachment to graphene, graphene oxide and carbon nanotubes. Tetrahedron Abstract.

Williams E, Pead S, Whiteman M, Wood ME, Wilson ID, Ladomery MR, Teklic T, Lisjak M, Hancock JT (2015). Detection of thiol modifications by hydrogen sulfide. , 555, 233-251. Abstract.

Tomasova L, Pavlovicova M, Malekova L, Misak A, Kristek F, Grman M, Cacanyiova S, Tomasek M, Tomaskova Z, Perry A, et al (2015). Effects of AP39, a novel triphenylphosphonium derivatised anethole dithiolethione hydrogen sulfide donor, on rat haemodynamic parameters and chloride and calcium Cav3 and RyR2 channels. Nitric Oxide, 46, 131-144. Abstract. Author URL.

Kulkarni-Chitnis M, Njie-Mbye YF, Mitchell L, Robinson J, Whiteman M, Wood ME, Opere CA, Ohia SE (2015). Inhibitory action of novel hydrogen sulfide donors on bovine isolated posterior ciliary arteries. Exp Eye Res, 134, 73-79. Abstract. Author URL.

Ikeda K, Marutani E, Hirai S, Wood ME, Whiteman M, Ichinose F (2015). Mitochondria-targeted hydrogen sulfide donor AP39 improves neurological outcomes after cardiac arrest in mice. Nitric Oxide - Biology and Chemistry, 49, 90-96. Abstract.

Whiteman M, Perry A, Zhou Z, Bucci M, Papapetropoulos A, Cirino G, Wood ME (2015). Phosphinodithioate and Phosphoramidodithioate Hydrogen Sulfide Donors. Handb Exp Pharmacol, 230, 337-363. Abstract. Author URL.

Penn TJ, Wood ME, Soanes DM, Csukai M, Corran AJ, Talbot NJ (2015). Protein kinase C is essential for viability of the rice blast fungus Magnaporthe oryzae. Mol Microbiol, 98(3), 403-419. Abstract. Author URL.

Szczesny B, Módis K, Yanagi K, Coletta C, Le Trionnaire S, Perry A, Wood ME, Whiteman M, Szabo C (2014). AP39, a novel mitochondria-targeted hydrogen sulfide donor, stimulates cellular bioenergetics, exerts cytoprotective effects and protects against the loss of mitochondrial DNA integrity in oxidatively stressed endothelial cells in vitro. Nitric Oxide, 41, 120-130. Abstract. Author URL.

McCook O, Radermacher P, Volani C, Asfar P, Ignatius A, Kemmler J, Möller P, Szabó C, Whiteman M, Wood ME, et al (2014). H2S during circulatory shock: some unresolved questions. Nitric Oxide, 41, 48-61. Abstract. Author URL.

Yang H-Y, Wu Z-Y, Wood M, Whiteman M, Bian J-S (2014). Hydrogen sulfide attenuates opioid dependence by suppression of adenylate cyclase/cAMP pathway. Antioxid Redox Signal, 20(1), 31-41. Abstract. Author URL.

Jamroz-Wiśniewska A, Gertler A, Solomon G, Wood ME, Whiteman M, Bełtowski J (2014). Leptin-induced endothelium-dependent vasorelaxation of peripheral arteries in lean and obese rats: role of nitric oxide and hydrogen sulfide. PLoS One, 9(1). Abstract. Author URL.

Le Trionnaire S, Perry A, Szczesny B, Szabo C, Winyard PG, Whatmore JL, Wood ME, Whiteman M (2014). The synthesis and functional evaluation of a mitochondria-targeted hydrogen sulfide donor, (10-oxo-10-(4-(3-thioxo-3H-1,2-dithiol-5-yl)phenoxy)decyl) triphenylphosphonium bromide (AP39). MedChemComm, 5(6), 728-736. Abstract.

Chitnis MK, Njie-Mbye YF, Opere CA, Wood ME, Whiteman M, Ohia SE (2013). Pharmacological actions of the slow release hydrogen sulfide donor GYY4137 on phenylephrine-induced tone in isolated bovine ciliary artery. Exp Eye Res, 116, 350-354.

Hydrogen sulfide (H2S), a colorless gas characterized by its pungent odor of rotten eggs has been reported to elicit relaxation effects on basal and pre-contracted non-ocular smooth muscles of several mammalian species. In the present study, we investigated the pharmacological actions of a H2S donor, GYY4137 on isolated bovine posterior ciliary artery after contraction with the adrenergic receptor agonist, phenylephrine. Furthermore, we studied the underlying mechanism of inhibitory action of GYY4137 on the posterior ciliary arteries. Isolated bovine posterior ciliary arteries were mounted in oxygenated organ baths and changes in isometric tension were measured with a Grass FT03 transducer connected to a recorder using a Grass Polyview Software. The relaxant actions of GYY4137 on phenylephrine pre-contracted arteries were observed in the absence and presence of an inhibitor of cyclo-oxygenase, flurbiprofen. Furthermore, the inhibitory effects of GYY4137 were studied in the absence or presence of inhibitors/activators of biosynthetic enzymes for H2S and nitric oxide production, as well as specific ion channel blockers. In the concentration range, 100 nM to 100 μM, GYY4137 elicited a concentration-dependant relaxation of phenylephrine-induced tone in isolated posterior ciliary arteries, with IC50 value of 13.4 ± 1.9 μM (n = 6). The cyclo-oxygenase inhibitor, flurbiprofen, significantly (p < 0.01) enhanced the relaxation induced by GYY4137 yielding IC50 value of 0.13 ± 0.08 μM (n = 6). Both the inhibitors of cystathionine β-synthase (aminooxyacetic acid, AOAA, 30 μM) and cystathionine γ-lyase (propargylglycine, PAG, 1 mM) caused significant (p < 0.05) rightward shifts in the concentration-response curve to GYY4137. Furthermore, the KATP channel antagonist, glibenclamide (100 μM) significantly (p < 0.01) attenuated the relaxant action induced by GYY4137 on bovine ciliary artery. Conversely, the activator of cystathionine β-synthase, SAM (100 μM) and an inhibitor of nitric oxide synthase, L-NAME (100 μM) had no significant effect on relaxations induced by GYY4137. We conclude that the inhibitory action of GYY4137 on isolated bovine ciliary artery is dependent upon the endogenous production of both prostanoids and H2S. Furthermore, the observed vascular smooth muscle relaxation induced by GYY4137 is mediated, at least in part, by KATP channels.

Abstract. Author URL.

Lencesova L, Hudecova S, Csaderova L, Markova J, Soltysova A, Pastorek M, Sedlak J, Wood ME, Whiteman M, Ondrias K, et al (2013). Sulphide signalling potentiates apoptosis through the up-regulation of IP3 receptor types 1 and 2. Acta Physiol (Oxf), 208(4), 350-361. Abstract. Author URL.

Wood ME, Bissiriou S, Lowe C, Windeatt KM (2013). Synthetic use of the primary kinetic isotope effect in hydrogen atom transfer 2: generation of captodatively stabilised radicals. Org Biomol Chem, 11(16), 2712-2723. Abstract. Author URL.

Li L, Fox B, Keeble J, Salto-Tellez M, Winyard PG, Wood ME, Moore PK, Whiteman M (2013). The complex effects of the slow-releasing hydrogen sulfide donor GYY4137 in a model of acute joint inflammation and in human cartilage cells. J Cell Mol Med, 17(3), 365-376. Abstract. Author URL.

Yong QC, Cheong JL, Hua F, Deng LW, Khoo YM, Lee HS, Perry A, Wood M, Whiteman M, Bian JS, et al (2012). Erratum: Regulation of heart function by endogenous gaseous mediators-crosstalk between nitric oxide and hydrogen sulfide (Antioxidants and Redox Signaling (2011) 14 (2081-2091)). Antioxidants and Redox Signaling, 16(7).

Lisjak M, Teklić T, Wilson ID, Wood M, Whiteman M, Hancock JT (2011). Hydrogen sulfide effects on stomatal apertures. Plant Signal Behav, 6(10), 1444-1446. Abstract. Author URL.

Lisjak M, Srivastava N, Teklic T, Civale L, Lewandowski K, Wilson I, Wood ME, Whiteman M, Hancock JT (2010). A novel hydrogen sulfide donor causes stomatal opening and reduces nitric oxide accumulation. Plant Physiol Biochem, 48(12), 931-935. Abstract. Author URL.

Cane‐Honeysett DJ, Dowle MD, Wood ME (2010). ChemInform Abstract: 1,2,4‐Dithiazolidine‐3,5‐dione: a Nucleophilic Isocyanate “Building Block”. ChemInform, 32(8), no-no.

BALDWIN JE, FRYER AM, PRITCHARD GJ, SPYVEE MR, WHITEHEAD RC, WOOD ME (2010). ChemInform Abstract: a Biomimetic Approach to the Pyridone Rings of the Acromelic Acids: a Concise Synthesis of Acromelic Acid a and an Approach to Acromelic Acid B. ChemInform, 29(41), no-no.

Gosain R, Norrish AM, Wood ME (2010). ChemInform Abstract: a Concise Method for the Functionalization of Ethanolamine α to Nitrogen Using Free Radical Methodology. ChemInform, 32(25), no-no.

SHIBATA N, BALDWIN JE, JACOBS A, WOOD ME (2010). ChemInform Abstract: a Stereocontrolled Synthesis of Protected (2R,3R)‐3‐Mercaptoaspartic Acid via a β‐Aspartyl Enolate Sulfenylation. ChemInform, 27(42), no-no.

BALDWIN JE, BAMFORD SJ, FRYER AM, WOOD ME (2010). ChemInform Abstract: a Versatile Approach to Acromelic Acid Analogues. ChemInform, 26(48), no-no.

BALDWIN JE, FRYER AM, PRITCHARD GJ, SPYVEE MR, WHITEHEAD RC, WOOD ME (2010). ChemInform Abstract: Concise Syntheses of Acromelic Acid a and Allo‐Acromelic Acid A. ChemInform, 29(19), no-no.

SHIBATA N, BALDWIN JE, JACOBS A, WOOD ME (2010). ChemInform Abstract: Electrophilic Sulfenylation in a Stereocontrolled Synthesis of Protected (2R,3R)‐3‐Mercaptoaspartic Acid from L‐Aspartic Acid. ChemInform, 28(4), no-no.

Gosain R, Norrish AM, Wood ME (2010). ChemInform Abstract: Free‐Radical Functionalization of β‐Amino Alcohols via 1,5‐Hydrogen Atom Abstraction in 1,3‐Oxazolidines. ChemInform, 30(50), no-no.

BALDWIN JE, FRYER AM, SPYVEE MR, WHITEHEAD RC, WOOD ME (2010). ChemInform Abstract: Stereocontrol in the Synthesis of Kainoids. ChemInform, 28(4), no-no.

BALDWIN JE, ADLINGTON RM, CROUCH NP, KEEPING JW, LEPPARD SW, PITLIK J, SCHOFIELD CJ, SOBEY WJ, WOOD ME (2010). ChemInform Abstract: Studies on the Mechanism of Deacetoxy‐Deacetylcephalosporin C Synthase Using Cyclopropyl Substituted Cephalosporin Probes. ChemInform, 23(10), no-no.

Wood ME, Fryer AM (2010). ChemInform Abstract: Synthesis of Kainoids and Kainoid Analogues. ChemInform, 30(24), no-no.

BALDWIN JE, BAMFORD SJ, FRYER AM, RUDOLPH MPW, WOOD ME (2010). ChemInform Abstract: Towards a Versatile Synthesis of Kainoids. Part 1. Introduction of the C‐3 and C‐4 Substituents. ChemInform, 28(32), no-no.

BALDWIN JE, BAMFORD SJ, FRYER AM, RUDOLPH MPW, WOOD ME (2010). ChemInform Abstract: Towards a Versatile Synthesis of Kainoids. Part 2. Two Methods for Establishment of C‐4 Stereochemistry. ChemInform, 28(32), no-no.

BALDWIN JE, FRYER AM, SPYVEE MR, WHITEHEAD RC, WOOD ME (2010). ChemInform Abstract: Towards a Versatile Synthesis of Kainoids. Part 3. Efficient Methods for Control of C‐4 Stereochemistry. ChemInform, 28(32), no-no.

Wood ME, Annis VM, Jones CD (2009). ChemInform Abstract: Unusual Reactivity of N‐Acyl Imides: N‐Aroyl‐1,2,4‐dithiazolidine‐3,5‐diones as Acyl Isocyanate Equivalents. ChemInform, 40(13), no-no.

Chowdhry MI, Horton PN, Hursthouse MB, Wood ME (2009). α-Allylation of α-amino acids via 1,5-hydrogen atom transfer. Tetrahedron Letters, 50(26), 3400-3403. Abstract.

Mark E. Wood, Sabine Bissiriou, Christopher Lowe and Kim M. Windeatt (2008). Investigations into the effectiveness of deuterium as a protecting group for C–H bonds in radical reactions involving hydrogen atom transfer. Organic and Biomolecular Chemistry, 6 Author URL.

Wood ME, Annis VM, Jones CD (2008). Unusual reactivity of N-acyl imides: N-aroyl-1,2,4-dithiazolidine-3,5-diones as acyl isocyanate equivalents. Org Biomol Chem, 6(22), 4099-4101. Abstract. Author URL.

Penny, M.J. Steere, J.S. Horton, P.N. (2006). "A General Route to Protected Quaternary alpha-Amino Acids from alpha-Amino Alcohols via a Stereocontrolled Radical Approach". Chemical Communications, 2983-2985.

Wood ME, Penny MJ, Steere JS, Horton PN, Light ME, Hursthouse MB (2006). A General Route to Protected Quaternary α‐Amino Acids from β‐Amino Alcohols via a Stereocontrolled Radical Approach. ChemInform, 37(49), no-no.

Cane‐Honeysett DJ, Dowle MD, Wood ME (2005). A Stereocontrolled Route to Protected Isocyanates from Alcohols. ChemInform, 36(26), no-no.

Dowle, M.D. Wood, M.E. (2005). A stereocontrolled route to protected isocyanates from alcohols. Tetrahedron, 61, 2141-2148.

Wood ME (2004). Tin Halides and Organotin Halides. ChemInform, 35(6), no-no.

Wood ME, Cane‐Honeysett DJ, Dowle MD (2003). 1,2,4‐Dithiazolidine‐3,5‐dione as an Isocyanate Equivalent in the Mitsunobu Reaction. ChemInform, 34(8), no-no.

Wood ME, Cane‐Honeysett DJ, Dowle MD, Coles SJ, Hursthouse MB (2003). Synthetic and Structural Studies on 1,2,4‐Dithiazolidine‐3,5‐dione Derivatives. ChemInform, 35(1), no-no.

Cane-Honeysett, D.J. Dowle, M.D. (2003). Synthetic and structural studies on 1,2,4-dithiazolidine-3,5-dione derivatives. Organic and Biomolecular Chemistry, 1, 3015-3023.

Cane-Honeysett, D.J. Dowle, M.D. (2002). 1,2,4-Dithiazolidine-3,5-dione as an isocyanate equivalent in the Mitsunobu reaction. Journal of the Chemical Society

Norrish, A.M. Wood, M.E. (2001). A concise method for the functionalisation of ethanolamine alpha-to nitrogen using free radical methodology. Tetrahedron, 57

Cane-Honeysett DJ, Dowle MD, Wood ME (2000). 1,2,4-Dithiazolidine-3,5-dione: a nucleophilic isocyanate 'building block'. Synlett(11), 1622-1624. Abstract.

Gosain R, Norrish AM, Wood ME (1999). Free-radical functionalisation of β-amino alcohols via 1,5-hydrogen atom abstraction in 1,3-oxazolidines. Tetrahedron Letters, 40(36), 6673-6676. Abstract.

Baldwin JE, Fryer AM, Pritchard GJ, Spyvee MR, Whitehead RC, Wood ME (1998). A biomimetic approach to the pyridone rings of the acromelic acids: a concise synthesis of acromelic acid a and an approach to acromelic acid B. Tetrahedron, 54(26), 7465-7484. Abstract.

Baldwin JE, Fryer AM, Pritchard GJ, Spyvee MR, Whitehead RC, Wood ME (1998). Concise syntheses of acromelic acid a and allo-acromelic acid A. Tetrahedron Letters, 39(7), 707-710. Abstract.

Baldwin JE, Adlington RM, Crouch NP, Hill RL, Wood ME, Lloyd MD (1997). Competing pathways in the oxidation of Z-3-ethylidine cephalosporin C by the enzyme deacetoxycephalosporin C synthase (DAOCS). Bioorganic and Medicinal Chemistry Letters, 7(5), 593-596. Abstract.

Shibata N, Baldwin JE, Wood ME (1997). Resin-bound peptide libraries showing specific metal ion binding. Bioorganic and Medicinal Chemistry Letters, 7(4), 413-416. Abstract.

Baldwin JE, Bamford SJ, Fryer AM, Rudolph MPW, Wood ME (1997). Towards a versatile synthesis of kainoids I: Introduction of the C-3 and C-4 substituents. Tetrahedron, 53(14), 5233-5254. Abstract.

Baldwin JE, Bamford SJ, Fryer AM, Rudolph MPW, Wood ME (1997). Towards a versatile synthesis of kainoids II: Two methods for establishment of C-4 stereochemistry. Tetrahedron, 53(14), 5255-5272. Abstract.

Baldwin JE, Fryer AM, Spyvee MR, Whitehead RC, Wood ME (1997). Towards a versatile synthesis of kainoids III: Efficient methods for control of C-4 stereochemistry. Tetrahedron, 53(14), 5273-5290. Abstract.

Shibata N, Baldwin JE, Jacobs A, Wood ME (1996). A Stereocontrolled Synthesis of Protected (2R, 3R)-3-Mercaptoaspartic Acid via a β-Aspartyl Enolate Sulfenylation. Synlett, 1996(6), 519-520. Abstract.

Shibata N, Baldwin JE, Jacobs A, Wood ME (1996). Electrophilic sulfenylation in a stereocontrolled synthesis of protected (2R,3R)-3-mercaptoaspartic acid from L-aspartic acid. Tetrahedron, 52(39), 12839-12852. Abstract.

Baldwin JE, Fryer AM, Spyvee MR, Whitehead RC, Wood ME (1996). Stereocontrol in the synthesis of kainoids. Tetrahedron Letters, 37(38), 6923-6924. Abstract.

BALDWIN JE, BAMFORD SJ, FRYER AM, WOOD ME (1995). A VERSATILE APPROACH TO ACROMELIC ACID ANALOGS. TETRAHEDRON LETTERS, 36(27), 4869-4872. Author URL.

Baldwin JE, Brown D, Scudder PH, Wood ME (1995). A chemical model for the activation of pyruvate-formate-lyase. Tetrahedron Letters, 36(12), 2105-2108. Abstract.

Baldwin JE, Bamford SJ, Fryer AM, Wood ME (1995). A versatile approach to acromelic acid analogues. Tetrahedron Letters, 36(27), 4869-4872.

Baldwin JE, Adlington RM, Crouch NP, Keeping JW, Leppard SW, Pitlik J, Schofield CJ, Sobey WJ, Wood ME (1991). Studies on the mechanism of deacetoxy-deacetylcephalosporin C synthase using cyclopropyl substituted cephalosporin probes. Journal of the Chemical Society, Chemical Communications(11), 768-770. Abstract.

Baldwin JE, Goh KC, Wood ME, Schofield CJ, Cooper RDG, Huffman GW (1991). The role of sulphur in cephalosporin biosynthesis. Bioorganic and Medicinal Chemistry Letters, 1(8), 421-424. Abstract.

Baldwin JE, Adlington RM, Russell MA, Schofield CJ, Wood ME (1989). Syntheses of [2‐13C] and [1,2‐13C] labelled α‐ketoglutaric acid. Journal of Labelled Compounds and Radiopharmaceuticals, 27(9), 1091-1099. Abstract.

Baldwin JE, Adlington RM, Schofield CJ, Sobey WJ, Wood ME (1989). The role of α-ketoglutarate in cephalosporin biosynthesis. Journal of the Chemical Society, Chemical Communications(15), 1012-1015. Abstract.

JONES JH, WOOD ME (1986). L-HISTIDINE BENZYL ESTER. SYNTHETIC COMMUNICATIONS, 16(12), 1515-1516. Author URL.

JONES JH, THOMAS DW, THOMAS RM, WOOD ME (1986). TERT-BUTYL CHLOROMETHYL ETHER. SYNTHETIC COMMUNICATIONS, 16(13), 1607-1610. Author URL.

Chapters

Wood ME (2007). 1,2,4‐Dithiazolidine‐3,5‐dione. In (Ed) Encyclopedia of Reagents for Organic Synthesis, Wiley.

Conferences

Torregrossa R, Wood M, Whiteman M (2020). Investigating the chemical reactivity, stability, and mechanisms of hydrogen sulfide (H2S) generation moieties commonly used in H2S-releasing drug hybrids. Author URL.

Pacitti D, Brown A, Torregrossa R, Kumar V, Balachandran L, Wood M, Jong Haw T, Hansbro N, Scotton CJ, Hansbro P, et al (2020). Mitochondria-targeted H2S suppresses and reverses cigarette smoke-induced inflammasome activity and lung injury in experimental COPD. 05.01 - Airway pharmacology and treatment.

Hansbro NG, Pacitti D, Brown A, Torregrossa R, Balachandran L, Kumar V, Wood M, Haw T-J, Scotton C, Whiteman M, et al (2020). Mitochondria-targeted Sulfide Delivery Molecules - New and Novel Players that can Suppress and Reverse Cigarette Smoke-induced Inflammasome Activity. Author URL.

Whiteman M, Pacitti D, Brown A, Torregrossa R, Balachandran L, Kumar V, Hansbro N, Wood ME, Haw TJ, Scotton C, et al (2020). Suppression and Reversal of Cigarette Smoke-Induced Inflammasome Activation/Activity and Lung Injury by Novel Mitochondria-Targeted Sulfide Delivery Molecules. Author URL.

Coavoy-Sanchez SA, Torregrossa R, Teixeira SA, Soares AG, Wood ME, Costa SP, Whiteman M, Muscara MN (2019). Effects of the mitochondria-targeted hydrogen sulfide (H2S) donor AP39 on atopic dermatitis in mice. Author URL.

Reburn C, Anayo L, Magnussen A, Perry A, Wood M, Curnow A (2019). Experimental findings utilising a new iron chelating ALA prodrug to enhance protoporphyrin IX-induced photodynamic therapy. Abstract.

Xiao AY, Brummett A, Maynard M, Pidikiti R, Miriyala S, Panchatcharam M, Sheibani N, Wood ME, Whiteman M, Harrison L, et al (2018). AP39, a Mitochondrial-Targeted Hydrogen Sulfide Donor, Protects Against Mitochondrial Dysfunction in Irradiated Mouse Retinal Endothelial Cells. Author URL.

Torregrossa R, Waters A, Gero D, Webb S, Rush C, Wood ME, Whiteman M (2017). Evaluation of a Novel Mitochondria-targeted Peptide-based H2S Donor Compound (RTP-10) in Hyperglycaemia-induced Microvascular Endothelial Cell Dysfunction. Author URL.

Allen C, Whatmore JL, Wood ME, Whiteman M, Bates DO (2017). Hydrogen sulfide as a novel therapeutic for diabetic retinopathy. Author URL.

Whiteman M, Karwi QG, Wood ME, Baxter GF (2017). Mitochondria-targeted Hydrogen Sulfide (H2S), but not Untargeted H2S, Reverses Ventricular Arrhythmia at Reperfusion. Author URL.

Etheridge T, Gaffney C, Szewczyk N, Torregrossa R, Wood ME, Whiteman M (2017). Mitochondria-targeting hydrogen sulfide donors prolong healthspan: lifespan ratio in Caenorhabditis elegans. Author URL.

Karwi QG, Whiteman M, Wood M, Baxter G (2017). Postconditioning with H2S donors: effect on reperfusion-induced ventricular arrhythmias. Author URL.

Waters A, Torregrossa R, Gero D, Perry A, Wood ME, Whiteman M (2017). RT01, a Novel Derivative of the Mitochondria-targeted Hydrogen Sulfide Donor AP39, Reversed Hyperglycaemia-induced Mitochondrial Dysfunction in Murine Brain Microvascular Endothelial Cells. Author URL.

Karwi QG, Whiteman M, Wood M, Baxter G (2017). The effect of hydrogen sulfide (H2S) on reperfusion-induced ventricular arrhythmias. Author URL.

Gero D, Torregrossa R, Waters A, Perry A, Wood ME, Whiteman M (2016). Mitochondria-Targeted Hydrogen Sulfide Donors Protect Microvascular Endothelial Cells from Hyperglycaemia-Induced Metabolic Changes and Oxidative Damage. Author URL.

Ahmad A, Olah G, Szczesny B, Wood ME, Whiteman M, Szabo C (2015). AP39, a mitochondrially targeted hydrogen sulfide donor, exerts protective effects in a rat model of renal ischemia-reperfusion. Author URL.

Schmidt TP, Lopes LB, Rodrigues L, Wood M, Whiteman M, Muscara MN, Costa SKP (2015). Antipsoriatic activity of GYY4137 (a slow-releasing hydrogen sulphide donor) microemulsion system using a mouse skin model of psoriasis. Author URL.

Chatzianastasiou A, Bibli SI, Wood ME, Whiteman M, Andreadou I, Manolopoulos VG, Papapetropoulos A (2015). Distinct mechanisms of cardioprotection by different H2S donors. Author URL.

Chatzianastasiou A, Bibli S-I, Wood ME, Whiteman M, Andreadou I, Manolopoulos VG, Papapetropoulos A (2015). Distinct mechanisms of cardioprotection by different hydrogen sulfide donors. Author URL.

Emerson M, Ilkan Z, Mustafa F, Solomon A, Wood ME, Whiteman M (2015). Inhibitory regulation of platelets by hydrogen sulphide. Author URL.

Alexander BE, Coles SJ, Khan TF, Maliszewsi J, Perry A, Pitak MP, Whiteman M, Wood ME (2015). Investigating the generation of hydrogen sulphide from the phosphinodithioate slow-release donor GYY4137: Novel products and experimental tools. Author URL.

Hedegaard ER, Gouliaev A, Winther AK, Aalling M, Sivasubramaniam N, Whiteman M, Skovgaard N, Simonsen U (2015). Involvement of K channels and calcium-independent mechanisms in hydrogen sulfide relaxation of rat mesenteric small arteries. Author URL.

Aboalsamh G, Saha M, Lobb I, Grewal J, Luke P, Wood M, Whiteman M, Sener A (2015). Mitochondrial Hydrogen Sulphide Donor Molecules Are More Effective Against Hypoxic Injury in Renal Tubular Epithelial Cells. Author URL.

Emerson M, Ahmad O, Rauzi F, Smyth E, Wood ME, Whiteman M (2015). Physiological regulation of platelet aggregation by the gasotransmitter hydrogen sulfide. Author URL.

Rodrigues L, Schmidt TR, Florenzano J, dos Santos KT, Cerqueira ARA, Teixeira SA, Wood ME, Whiteman M, Muscara MN, Costa SKP, et al (2015). The slow-releasing hydrogen sulphide donor, GYY4137, exhibits novel anti-skin symptoms of psoriasis and related itch. Author URL.

Szczesny B, Modis K, Yanagi K, Le Trionnaire S, Wood ME, Whiteman M, Szabo C (2014). Cytoprotective effects of AP39, a mitochondrially targeted hydrogen sulfide donor in oxidatively stressed endothelial cells: Protection against the loss of cell viability and bioenergetics and attenuation of mitochondrial DNA injury. Author URL.

Hafner S, Matallo J, Groeger M, Wachter U, McCook O, Wood M, Whiteman M, Georgieff M, Calzia E, Radermacher P, et al (2014). EFFECTS OF THE SLOW-RELEASING SULFIDE DONOR GYY4137 DURING RESUSCITATED SEPTIC SHOCK IN ATHEROSCLEROTIC SWINE. Author URL.

Tomasova L, Misak A, Kristek F, Perry A, Wood ME, Ondrias K, Whiteman M (2014). Effects of a Novel Triphenylphosphonium Derivatised Anethole Dithiolethione Hydrogen Sulfide (H2S) Donor, AP39, on Cardiac Ion Channels and on Haemodynamic Parameters in Normotensive and Hypertensive Rats in Vivo. Author URL.

Whiteman M, Perry A, Wood ME (2014). H2S in inflammation: Time for resolution?. Author URL.

Jeney V, Potor L, Petho D, Whiteman M, Wood ME, Balla G, Balla J (2014). HYDROGEN-SULFIDE RELEASING MOLECULES INHIBIT INTRAPLAQUE HEMORRHAGE-ASSOCIATED OXIDATIVE BURST IN THE HUMAN ATHEROMA AND SUBSEQUENT ENDOTHELIAL REACTIONS. Author URL.

Szczesny B, Wood ME, Whiteman M, Szabo C (2014). Hydrogen Sulfide is an Endogenous Stimulator of Mitochondrial DNA Repair. Author URL.

Jeney V, Potor L, Petho D, Whiteman M, Wood ME, Balla G, Balla J (2014). Hydrogen-sulfide releasing molecules inhibit intraplaque hemorrhage-associated oxidative burst in the human atheroma and subsequent endothelial reactions. Author URL.

Emerson M, Solomon A, Smyth E, Wood ME, Whiteman M (2014). Inhibition of platelet aggregation in vitro and in vivo by the H2S releasing compound GYY4137. Author URL.

Gero D, Szczesny B, Modis K, Yanagi K, Wood ME, Perry A, Szabo C, Whiteman M (2014). Mitochondira-targeted hydrogen sulfide donors AP39 and AP123 attenuate hyperglycaemia-induced oxidative stress and loss of bioenergetics in microvascular endothelial cells. Author URL.

Gero D, Szczesny B, Perry A, Modis K, Wood ME, Szabo C, Whiteman M (2014). Novel Mitochondria-Targeted Hydrogen Sulfide (H2S) Donors AP39 and AP123 Attenuate Hyperglycaemia-Induced Oxidative Stress and Loss of Bioenergetics in Microvascular Endothelial Cells. Author URL.

Ferguson D, Perry A, Wood ME, Winyard PG, Whiteman M (2014). Potentiation of Methyl Aminolevulinate (MAL)-Induced Photodynamic Therapy (PDT) Killing of Skin Cancer Cells by Mitochondria-Targeted Hydrogen Sulfide (H2S) Donors. Author URL.

Fox B, Holland T, Wood ME, Winyard PG, Whiteman M (2013). Comparing the differential effects of novel, slow-release H2S donors on inflammatory mediators and cell proliferation in human joint and immune cells. Author URL.

Rodrigues L, Santos BC, Florenzano J, dos Santos KT, Lopes KC, Lira FBC, Teixeira SA, Wood ME, Whiteman M, Muscara MN, et al (2013). Does the slow-releasing hydrogen sulfide donor GYY4137 controls inflammation and pruritogen responses in mouse skin?. Author URL.

Malekova L, Pavlovicova M, Kristek F, Tomasova L, Wood ME, Whiteman M, Ondrias K (2013). Effects of H2S-donors on membrane channels. Author URL.

Radermacher P, McCook O, Asfar P, Calzia E, Wood ME, Szabo C, Whiteman M, Wang R (2013). Expression of H2S-catalyzing enzymes during "acute chronic disease". Author URL.

Le Trionnaire S, Perry A, Whatmore JL, Wood ME, Whiteman M (2013). Mitochondria-targeted hydrogen sulfide donors: a novel twist to an old "tail"?. Author URL.

Whiteman M, Perry A, Le Trionnaire S, Whatmore JL, Ahmed T, Fox B, Kerr P, Haigh R, Winyard PG, Wood ME, et al (2013). Modulation of inflammatory and vascular signalling by novel slow release and mitochondria-targeted H2S donors. Author URL.

Jeney V, Potor L, Whiteman M, Wood ME, Balla G, Balla J (2013). Potential anti-atherogenic effects of hydrogen-sulfide releasing molecules. Author URL.

Whatmore JL, Wolanska KI, Perry A, Wood ME, Whiteman M (2013). Slow release hydrogen sulfide (H2S) donors prevent hyperglycaemia-induced glycocalyx loss in retinal mirovascular endothelial cells. Author URL.

Lencesova L, Hudecova S, Markova J, Soltysova A, Sedlak J, Wood ME, Whiteman M, Ondrias K, Krizanova O (2013). Sulfide signalling potentiates apoptosis through the up-regulation of IP3 receptors type 1 and 2. Author URL.

Lisjak M, Teklic T, Wilson I, Wood ME, Whiteman M, Spoljarevic M, Hancock JT (2013). The role of H2S in pepper leaves under salt stress conditions. Author URL.

Fox B, Perry A, Winyard P, Wood ME, Whiteman M (2012). Characterising the effect of novel slow-release H2S donors on pro-inflammatory enzyme activity in human cartilage cells. Author URL.

Fox B, Holland T, Perry A, Wood ME, Whiteman M (2012). Characterising the effect of novel slow-release H2S donors on pro-inflammatory enzyme activity in human cartilage cells. Author URL.

Fox B, Holland T, Perry A, Winyard PG, Wood ME, Whiteman M (2012). Defining the Effect of Novel Slow-Release H2S Donors on Pro-Inflammatory Mediators and Enzymes in Human Joint Cells. Author URL.

Wolanska K, Perry A, Wood ME, Chibber R, Whatmore J, Whiteman M (2012). Hydrogen sulfide - a novel guardian of the endothelial glycocalyx?. Author URL.

Le Trionnaire S, Perry A, Whatmore JL, Winyard PG, Wood ME, Whiteman M (2012). Mitochondria-Targeted Slow Release Hydrogen Donors: a Novel Link to an Old 'tail'?. Author URL.

Lo Faro ML, Whatmore J, More J, Wood ME, Whiteman M, Winyard PG (2012). Mutual regulation of •NO/H2S bioavailability and cell signalling in the cardiovascular system. Author URL.

Le Trionnaire S, Whatmore J, Perry A, Wood ME, Matthew W (2012). Slow release H2S donors protect human microvascular endothelial cells from oxidative stress induced cell death: Markedly increased potency by mitochondria-targeting. Author URL.

Le Trionnaire S, Whatmore JL, Perry A, Wood ME, Whiteman M (2012). Slow release H2S donors protect human microvascular endothelial cells from oxidative stress induced cell death: Markedly increased potency by mitochondria-targetting. Author URL.

Fox B, Li L, Keeble J, Winyard P, Wood M, Moore P, Whiteman M (2012). The complex effects of a slow-releasing hydrogen sulifde donor (GYY4137) in a model of inflammatory arthritis and in primary human cartilage cells. Author URL.

Le Trionnaire S, Whatmore JL, Perry A, Wood ME, Whiteman M (2011). Endogenous hydrogen sulfide (H2 S) and novel slow release H2S donors protect human endothelial cells from oxidative stress-induced cell death. Author URL.

Le Trionnaire S, Whatmore J, Perry A, Wood ME, Whiteman M (2011). Endogenous hydrogen sulphide (H2S) and novel slow release H2S donors protect human microvascular endothelial cells from oxidative stress-induced cell death. Author URL.

Chopra M, Perry A, Hodgkinson A, Wood ME, Whiteman M (2010). Contrasting Effects of 'Fast' and 'Slow' Releasing H2S Donors on β Cell Viability in the Diabetic Milieu. Author URL.

Whiteman M, Chopra M, Wood ME, Whatmore JL (2010). ENDOGENOUS HYDROGEN SULFIDE (H2S) AND NOVEL SLOW RELEASING H2S DONOR COMPOUNDS INHIBIT ENDOTHELIAL DYSFUNCTION INDUCED BY TNF- α, OXIDATIVE AND NITROSATIVE STRESS. Author URL.

Perry MM, Hui C, Whiteman M, Wood ME, Adcock I, Kirkham P, Chung KF (2010). Hydrogen Sulfide Inhibits Proliferation and Release of IL-8 from Human Airway Smooth Muscle Cells. Author URL.

Whiteman M, Wood ME, Whatmore JL (2010). Novel Slow Releasing Hydrogen Sulfide (H2S) Donor Compounds Inhibit Endothelial Dysfunction Induced by TNF-α, Oxidative and Nitrosative Stress. Author URL.

Publications by year

In Press

2022

2021

Torregrossa R (2021). Synthesis and Basic in Vitro Characterisation of Novel Mitochondria-Targeted Hydrogen Sulfide Delivering Molecules.

Hydrogen sulfide (H2S) is a human physiological mediator, enzymatically produced primarily in the mitochondria. Its administration in vitro or in vivo ameliorates mitochondrial dysfunction. Mitochondria-targeted H2S donor compounds were previously synthesised by coupling two H2S donor moieties (ADTOMe and HTB) to a known mitochondrial-targeting moiety, making AP39 and AP123, respectively. Although AP39 was effective against mitochondrial dysfunction in vitro and in vivo, its efficacy and tolerability may be improved by appropriate changes in its structure. Thus, in this work, new donors were generated by using a new donor moiety, by changing the linking approach or using a different targeting compound. Another approach to deliver H2S donor moieties inside the mitochondria, independently from the mitochondrial potential, was explored, using a known a tetrapeptide, therefore, RTP10 and RTP12 were synthesised. The H2S-releasing molecules were also linked to a compound known for its beneficial properties towards mitochondrial bioenergetics. Although the novel compounds synthesised reduced mitochondrial dysfunction more efficiently than their non-bonded equivalent control compounds, in an in vitro hyperglycaemia-induced model, only four novel molecules exerted an improvement in AP39/AP123 tolerability and had comparable efficacy thus, they might be further evaluated as drug candidates.
Another compound was synthesised using a different approach for delivering H2S in cells. The compound was evaluated in a few cell dysfunction models, in which it showed promising results.
Furthermore, studies on the stability, the reactivity and the possible H2S generation mechanism of three H2S donor moieties commonly used in H2S-releasing drug hybrids were conducted, identifying the conditions under which they may react. Indeed, despite their biological effects being widely studied, the chemical mechanisms by which they may generate H2S have never been appropriately investigated and their metabolites have never been properly characterised. Here, studies on the identification of the possible metabolites of the three donors were conducted and their activity was evaluated in the same in vitro model, in which they did not exert significant beneficial effects. Also, they did not cause toxicity at the active concentration range of their corresponding donor. The main decomposition products of ADTOMe were identified as ADOMe, plus the carboxylic acid and ketone derivatives. HTB generated primarily, the corresponding nitrile, in addition to the corresponding carboxylic acid and amide. ADOMe may form the corresponding carboxylic acid and ketone and it may also react with thiols, forming a sulfur-sulfur bond. ADTOMe, HTB and ADOMe are stable at room temperature in water/DMSO solutions. They are stable at harsh acidic pH and at pH = 8 but are susceptible to hydrolysis at strong basic pH. ADTOMe and HTB but not ADOMe, are reactive in presence of hydrogen peroxide.

Abstract.

2020

Hansbro NG, Pacitti D, Brown A, Torregrossa R, Balachandran L, Kumar V, Wood M, Haw T-J, Scotton C, Whiteman M, et al (2020). Mitochondria-targeted Sulfide Delivery Molecules - New and Novel Players that can Suppress and Reverse Cigarette Smoke-induced Inflammasome Activity. Author URL.

2019

2018

2017

Allen C, Whatmore JL, Wood ME, Whiteman M, Bates DO (2017). Hydrogen sulfide as a novel therapeutic for diabetic retinopathy. Author URL.

Karwi QG, Whiteman M, Wood M, Baxter G (2017). Postconditioning with H2S donors: effect on reperfusion-induced ventricular arrhythmias. Author URL.

Karwi QG, Whiteman M, Wood M, Baxter G (2017). The effect of hydrogen sulfide (H2S) on reperfusion-induced ventricular arrhythmias. Author URL.

2016

Abstract.

Abstract. Author URL.

2015

Williams E, Pead S, Whiteman M, Wood ME, Wilson ID, Ladomery MR, Teklic T, Lisjak M, Hancock JT (2015). Detection of thiol modifications by hydrogen sulfide. , 555, 233-251. Abstract.

Chatzianastasiou A, Bibli SI, Wood ME, Whiteman M, Andreadou I, Manolopoulos VG, Papapetropoulos A (2015). Distinct mechanisms of cardioprotection by different H2S donors. Author URL.

Emerson M, Ilkan Z, Mustafa F, Solomon A, Wood ME, Whiteman M (2015). Inhibitory regulation of platelets by hydrogen sulphide. Author URL.

Emerson M, Ahmad O, Rauzi F, Smyth E, Wood ME, Whiteman M (2015). Physiological regulation of platelet aggregation by the gasotransmitter hydrogen sulfide. Author URL.

2014

Whiteman M, Perry A, Wood ME (2014). H2S in inflammation: Time for resolution?. Author URL.

Szczesny B, Wood ME, Whiteman M, Szabo C (2014). Hydrogen Sulfide is an Endogenous Stimulator of Mitochondrial DNA Repair. Author URL.

Emerson M, Solomon A, Smyth E, Wood ME, Whiteman M (2014). Inhibition of platelet aggregation in vitro and in vivo by the H2S releasing compound GYY4137. Author URL.

2013

Malekova L, Pavlovicova M, Kristek F, Tomasova L, Wood ME, Whiteman M, Ondrias K (2013). Effects of H2S-donors on membrane channels. Author URL.

Radermacher P, McCook O, Asfar P, Calzia E, Wood ME, Szabo C, Whiteman M, Wang R (2013). Expression of H2S-catalyzing enzymes during "acute chronic disease". Author URL.

Le Trionnaire S, Perry A, Whatmore JL, Wood ME, Whiteman M (2013). Mitochondria-targeted hydrogen sulfide donors: a novel twist to an old "tail"?. Author URL.

Abstract. Author URL.

Jeney V, Potor L, Whiteman M, Wood ME, Balla G, Balla J (2013). Potential anti-atherogenic effects of hydrogen-sulfide releasing molecules. Author URL.

Lisjak M, Teklic T, Wilson I, Wood ME, Whiteman M, Spoljarevic M, Hancock JT (2013). The role of H2S in pepper leaves under salt stress conditions. Author URL.

2012

Whiteman ML, Wood ME, Perry A (2012). Compounds for use in the treatment of plants. Abstract. Author URL.

Wolanska K, Perry A, Wood ME, Chibber R, Whatmore J, Whiteman M (2012). Hydrogen sulfide - a novel guardian of the endothelial glycocalyx?. Author URL.

Le Trionnaire S, Perry A, Whatmore JL, Winyard PG, Wood ME, Whiteman M (2012). Mitochondria-Targeted Slow Release Hydrogen Donors: a Novel Link to an Old 'tail'?. Author URL.

2011

Lisjak M, Teklić T, Wilson ID, Wood M, Whiteman M, Hancock JT (2011). Hydrogen sulfide effects on stomatal apertures. Plant Signal Behav, 6(10), 1444-1446. Abstract. Author URL.

2010