Imperial College London

Professor Matthew J. Fuchter

Faculty of Natural SciencesDepartment of Chemistry

Professor of Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 5815m.fuchter

 
 
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Location

 

401CMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Publication Type
Year
to

109 results found

Davidson RWM, Fuchter MJ, 2016, Direct NHC-catalysed redox amidation using CO2 for traceless masking of amine nucleophiles, Chemical Communications, Vol: 52, Pages: 11638-11641, ISSN: 1364-548X

The N-heterocyclic carbene (NHC)-catalysed redox amidation reaction is poorly developed and usually requires catalytic co-additives for electron-rich amine nucleophiles. We report a masking strategy (using CO2) that couples release of the free amine nucleophile to catalytic turnover, and in doing so, enables direct catalytic redox amidation of electron-rich amines.

Journal article

Brandt JR, Wang X, Yang Y, Campbell A, Fuchter MJet al., 2016, Circularly Polarized Phosphorescent Electroluminescence with a High Dissymmetry Factor from PHOLEDs Based on a Platinahelicene, Journal of the American Chemical Society, Vol: 138, Pages: 9743-9746, ISSN: 1520-5126

Circularly polarized (CP) light is of interest inareas such as quantum optical computing, optical spintronics,biomedicine and high efficiency displays. Direct emissionof CP light from organic light-emitting diodes (OLEDs) hasbeen a focus of research as it has the immediate applicationof increasing efficiency and simplifying device architecture inOLED based displays. High dissymmetry (gEL) factor valueshave been reported for devices employing fluorescent polymers,but these CP-OLEDs are limited in their ultimate efficienciesby the type of emissive electronic transitions involved.In contrast, phosphorescent OLEDs (PHOLEDs) canemit light from triplet excited states and can thereforeachieve very high efficiencies. However, CP-PHOLEDs aresignificantly understudied and the two previous reports sufferedfrom very low brightness or gEL values. Here, we use aplatinahelicene complex to construct a CP-PHOLED thatachieves both a display level brightness and a high gEL factor.The dissymmetry of CP emission reached with this proof-ofconceptsingle-layer helicene-based device is sufficient toprovide real-world benefits over non-polarized emission, andpaves the way towards chiral metal complex–based CPPHOLEDdisplays.

Journal article

Fuchter MJ, Weston CE, Richardson RD, 2016, Photoswitchable basicity through the use of azoheteroarenes, Chemical Communications, Vol: 52, Pages: 4521-4524, ISSN: 1364-548X

Azoheteroarene photoswitches offer functional advantages over their more conventional azobenzene counterparts by virtue of their heteroaromatic ring(s). Here we report that azobis(2-imidazole) functions as a photoswitchable base due to the additional proton stabilisation that is possible in the protonated Z isomer, facilitated by the basic imidazole nitrogens. This thermodynamic difference in stability corresponds to a 1.3 unit difference in pKa values between the E and Z isomers. This pKa difference can be used to reversibly control solution pH.

Journal article

Chen PB, Ding S, Zanghì G, Soulard V, DiMaggio PA, Fuchter MJ, Mecheri S, Mazier D, Scherf A, Malmquist NAet al., 2016, Plasmodium falciparum PfSET7: enzymatic characterization and cellular localization of a novel protein methyltransferase in sporozoite, liver and erythrocytic stage parasites., Scientific Reports, Vol: 6, ISSN: 2045-2322

Epigenetic control via reversible histone methylation regulates transcriptional activation throughout the malaria parasite genome, controls the repression of multi-copy virulence gene families and determines sexual stage commitment. Plasmodium falciparum encodes ten predicted SET domain-containing protein methyltransferases, six of which have been shown to be refractory to knock-out in blood stage parasites. We have expressed and purified the first recombinant malaria methyltransferase in sufficient quantities to perform a full enzymatic characterization and reveal the ill-defined PfSET7 is an AdoMet-dependent histone H3 lysine methyltransferase with highest activity towards lysines 4 and 9. Steady-state kinetics of the PfSET7 enzyme are similar to previously characterized histone methyltransferase enzymes from other organisms, however, PfSET7 displays specific protein substrate preference towards nucleosomes with pre-existing histone H3 lysine 14 acetylation. Interestingly, PfSET7 localizes to distinct cytoplasmic foci adjacent to the nucleus in erythrocytic and liver stage parasites, and throughout the cytoplasm in salivary gland sporozoites. Characterized recombinant PfSET7 now allows for target based inhibitor discovery. Specific PfSET7 inhibitors can aid in further investigating the biological role of this specific methyltransferase in transmission, hepatic and blood stage parasites, and may ultimately lead to the development of suitable antimalarial drug candidates against this novel class of essential parasite enzymes.

Journal article

Fuchter MJ, 2015, Young Career Focus: Dr. Matthew J. Fuchter (Imperial College London, UK), SYNTHESIS-STUTTGART, Vol: 47, Pages: A152-A155, ISSN: 0039-7881

Journal article

Curry E, Green I, Chapman-Rothe N, Shamsaei E, Kandil S, Cherblanc F, Payne L, Bell E, Ganesh T, Srimongkolpithak N, Caron J, Li F, Uren AG, Snyder JP, Vedadi M, Fuchter MJ, Brown Ret al., 2015, Dual EZH2 and EHMT2 histone methyltransferase inhibition increases biological efficacy in breast cancer cells, Clinical Epigenetics, Vol: 7, ISSN: 1868-7083

Background: Many cancers show aberrant silencing of gene expression andoverexpression of histone methyltransferases. The histone methyltransferases (HKMT)EZH2 and EHMT2 maintain the repressive chromatin histone marks H3K27 and H3K9methylation respectively, which are associated with transcriptional silencing. Althoughselective HKMT inhibitors reduce levels of individual repressive marks, removal ofH3K27me3 by specific EZH2 inhibitors, for instance, may not be sufficient for inducingexpression of genes with multiple repressive marks.Results: We report that gene expression and inhibition of triple negative breast cancer cellgrowth (MDA-MB-231) are markedly increased when targeting both EZH2 and EHMT2,either by siRNA knockdown or pharmacological inhibition, rather than independently. Indeed,expression of certain genes is only induced upon dual inhibition. We sought to identifycompounds which showed evidence of dual EZH2 and EHMT2 inhibition. Using a cell-basedassay, based on the substrate-competitive EHMT2 inhibitor BIX01294, we have identifiedproof-of-concept compounds that induce re-expression of a subset of genes consistent withdual HKMT inhibition. Chromatin immunoprecipitation verified a decrease in silencing marksand an increase in permissive marks at the promoter and transcription start site of reexpressedgenes, while Western analysis showed reduction in global levels of H3K27me3and H3K9me3. The compounds inhibit growth in a panel of breast cancer and lymphoma celllines with low to sub-micromolar IC50s. Biochemically, the compounds are substratecompetitive inhibitors against both EZH2 and EHMT1/2.Conclusions: We have demonstrated that dual inhibition of EZH2 and EHMT2 is moreeffective at eliciting biological responses of gene transcription and cancer cell growthinhibition compared to inhibition of single HKMTs, and we report the first dual EZH2-EHMT1/2 substrate competitive inhibitors that are functional in cells.

Journal article

Scott DJ, Simmons TR, Lawrence EJ, Wildgoose GG, Fuchter MJ, Ashley AEet al., 2015, Facile Protocol for Water-Tolerant "Frustrated Lewis Pair"-Catalyzed Hydrogenation, ACS Catalysis, Vol: 5, Pages: 5540-5544, ISSN: 2155-5435

Despite rapid advances in the field of metal-free, “frustrated Lewis pair” (FLP)-catalyzed hydrogenation, the need for strictly anhydrous reaction conditions has hampered wide-scale uptake of this methodology. Herein, we report that, despite the generally perceived moisture sensitivity of FLPs, 1,4-dioxane solutions of B(C6F5)3 actually show appreciable moisture tolerance and can catalyze hydrogenation of a range of weakly basic substrates without the need for rigorously inert conditions. In particular, reactions can be performed directly in commercially available nonanhydrous solvents without subsequent drying or use of internal desiccants.

Journal article

Bultinck P, Cherblanc FL, Fuchter MJ, Herrebout WA, Lo Y-P, Rzepa HS, Siligardi G, Weimar Met al., 2015, Chiroptical Studies on Brevianamide B: Vibrational and Electronic Circular Dichroism Confronted, JOURNAL OF ORGANIC CHEMISTRY, Vol: 80, Pages: 3359-3367, ISSN: 0022-3263

Journal article

Fuchter MJ, 2015, Carbon-14 reprocessing at cardiff, Publisher: WILEY-BLACKWELL, Pages: 149-150, ISSN: 0362-4803

Conference paper

Anwar A, Archibald S, Audisio D, Badman G, Bergin J, Bew SP, Bloom J, Bushby N, Busigin A, Chan MY, Davies J, Dilworth J, Dunscombe M, Elmore CS, Engstrom P, Fuchter MJ, Geach NJ, Georgin D, Griffiths A, Hansen P, Hardcastle G, Hiatt-Gipson GD, Hickey MJ, Kitson SL, Lashford A, Lenz E, Lewinton S, Lockley WJ, Loreau O, Maddocks S, Marlière P, McEwen A, Moody TS, Morgan P, Roe SJ, Schenk DJ, Speed DJ, Stockman RA, Sumal K, Taran F, Thurston S, Waring M, Watters WHet al., 2015, Abstracts., J Labelled Comp Radiopharm, Vol: 58, Pages: 147-155

Journal article

Malmquist NA, Sundriyal S, Caron J, Chen P, Witkowski B, Menard D, Suwanarusk R, Renia L, Nosten F, Belen Jimenez-Diaz M, Angulo-Barturen I, Santos Maritnez M, Ferrer S, Sanz LM, Gamo F-J, Wittlin S, Duffy S, Avery VM, Ruecker A, Delves MJ, Sinden RE, Fuchter MJ, Scherf Aet al., 2015, Histone Methyltransferase Inhibitors Are Orally Bioavailable, Fast-Acting Molecules with Activity against Different Species Causing Malaria in Humans, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol: 59, Pages: 950-959, ISSN: 0066-4804

Journal article

Udemba A, Smith G, Nguyen Q-D, Kaliszczak M, Carroll L, Fortt R, Fuchter MJ, Aboagye EOet al., 2015, Design, synthesis and initial characterisation of a radiolabelled [F-18]pyrimidoindolone probe for detecting activated caspase-3/7, ORGANIC & BIOMOLECULAR CHEMISTRY, Vol: 13, Pages: 5418-5423, ISSN: 1477-0520

Journal article

Di Fruscia P, Zacharioudakis E, Liu C, Moniot S, Laohasinnarong S, Khongkow M, Harrison IF, Koltsida K, Reynolds CR, Schmidtkunz K, Jung M, Chapman KL, Steegborn C, Dexter DT, Sternberg MJE, Lam EW-F, Fuchter MJet al., 2015, The Discovery of a Highly Selective 5,6,7,8-Tetrahydrobenzo[4,5]thieno[ 2,3-d] pyrimidin-4(3H)-one SIRT2 Inhibitor that is Neuroprotective in an in vitro Parkinson's Disease Model, CHEMMEDCHEM, Vol: 10, Pages: 69-82, ISSN: 1860-7179

Journal article

Richardson RD, Baud MGJ, Weston CE, Rzepa HS, Kuimova MK, Fuchter MJet al., 2015, Dual wavelength asymmetric photochemical synthesis with circularly polarized light, Chemical Science, Vol: 6, Pages: 3853-3862, ISSN: 2041-6539

Journal article

Scott DJ, Fuchter MJ, Ashley AE, 2014, Nonmetal Catalyzed Hydrogenation of Carbonyl Compounds, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 136, Pages: 15813-15816, ISSN: 0002-7863

Journal article

Forkel NV, Henderson DA, Fuchter MJ, 2014, Calcium-mediated stereoselective reduction of alpha,beta-epoxy ketones, TETRAHEDRON LETTERS, Vol: 55, Pages: 5511-5514, ISSN: 0040-4039

Journal article

Sundriyal S, Malmquist NA, Caron J, Blundell S, Liu F, Chen X, Srimongkolpithak N, Jin J, Charman SA, Scherf A, Fuchter MJet al., 2014, Development of Diaminoquinazoline Histone Lysine Methyltransferase Inhibitors as Potent Blood-Stage Antimalarial Compounds, CHEMMEDCHEM, Vol: 9, Pages: 2360-2373, ISSN: 1860-7179

Journal article

Scott DJ, Fuchter MJ, Ashley AE, 2014, Metal-Free Hydrogenation Catalyzed by an Air-Stable Borane: Use of Solvent as a Frustrated Lewis Base, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 53, Pages: 10218-10222, ISSN: 1433-7851

Journal article

Meyners C, Baud MGJ, Fuchter MJ, Meyer-Almes F-Jet al., 2014, Kinetic method for the large-scale analysis of the binding mechanism of histone deacetylase inhibitors, ANALYTICAL BIOCHEMISTRY, Vol: 460, Pages: 39-46, ISSN: 0003-2697

Journal article

Weston CE, Richardson RD, Haycock PR, White AJP, Fuchter MJet al., 2014, Arylazopyrazoles: Azoheteroarene Photoswitches Offering Quantitative Isomerization and Long Thermal Half-Lives, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 136, Pages: 11878-11881, ISSN: 0002-7863

Journal article

Dembele L, Franetich J-F, Lorthiois A, Gego A, Zeeman A-M, Kocken CHM, Le Grand R, Dereuddre-Bosquet N, van Gemert G-J, Sauerwein R, Vaillant J-C, Hannoun L, Fuchter MJ, Diagana TT, Malmquist NA, Scherf A, Snounou G, Mazier Det al., 2014, Persistence and activation of malaria hypnozoites in long-term primary hepatocyte cultures, NATURE MEDICINE, Vol: 20, Pages: 307-312, ISSN: 1078-8956

Journal article

Meyners C, Baud MGJ, Fuchter MJ, Meyer Almes F-Jet al., 2014, Thermodynamics of ligand binding to histone deacetylase like amidohydrolase from Bordetella/Alcaligenes, Journal of Molecular Recognition, Vol: 27, Pages: 160-172

Journal article

Berger RJF, Fuchter MJ, Krossing I, Rzepa HS, Schaefer J, Scherer Het al., 2014, Gold(I) mediated rearrangement of [7]-helicene to give a benzo[cd]pyrenium cation embedded in a chiral framework, CHEMICAL COMMUNICATIONS, Vol: 50, Pages: 5251-5253, ISSN: 1359-7345

Journal article

Srimongkolpithak N, Sundriyal S, Li F, Vedadi M, Fuchter MJet al., 2014, Identification of 2,4-diamino-6,7-dimethoxyquinoline derivatives as G9a inhibitors, MEDCHEMCOMM, Vol: 5, Pages: 1821-1828, ISSN: 2040-2503

Journal article

Cherblanc FL, Lo Y-P, Herrebout WA, Bultinck P, Rzepa HS, Fuchter MJet al., 2013, Mechanistic and Chiroptical Studies on the Desulfurization of Epidithiodioxopiperazines Reveal Universal Retention of Configuration at the Bridgehead Carbon Atoms, JOURNAL OF ORGANIC CHEMISTRY, Vol: 78, Pages: 11646-11655, ISSN: 0022-3263

Journal article

Cherblanc FL, Chapman KL, Reid J, Borg AJ, Sundriyal S, Alcazar-Fuoli L, Bignell E, Demetriades M, Schofield CJ, DiMaggio PA, Brown R, Fuchter MJet al., 2013, On the Histone Lysine Methyltransferase Activity of Fungal Metabolite Chaetocin, JOURNAL OF MEDICINAL CHEMISTRY, Vol: 56, Pages: 8616-8625, ISSN: 0022-2623

Journal article

Judge DK, Haycock P, Richardson RD, Fuchter MJet al., 2013, ortho-Substituted 1,8-Diarylnaphthalenes: Conformational Thermodynamics and Kinetics, SYNLETT, Vol: 24, Pages: 2365-2369, ISSN: 0936-5214

Journal article

Kaliszczak M, Patel H, Kroll SHB, Carroll L, Smith G, Delaney S, Heathcote DA, Bondke A, Fuchter MJ, Coombes RC, Barrett AGM, Ali S, Aboagye EOet al., 2013, Development of a cyclin-dependent kinase inhibitor devoid of ABC transporter-dependent drug resistance, British Journal of Cancer, Vol: 109, Pages: 2356-2367, ISSN: 1532-1827

background: Cyclin-dependent kinases (CDKs) control cell cycle progression, RNA transcription and apoptosis, making them attractive targets for anticancer drug development. Unfortunately, CDK inhibitors developed to date have demonstrated variable efficacy.methods: We generated drug-resistant cells by continuous low-dose exposure to a model pyrazolo[1,5-a]pyrimidine CDK inhibitor and investigated potential structural alterations for optimal efficacy.results: We identified induction of the ATP-binding cassette (ABC) transporters, ABCB1 and ABCG2, in resistant cells. Assessment of features involved in the ABC transporter substrate specificity from a compound library revealed high polar surface area (>100 Å2) as a key determinant of transporter interaction. We developed ICEC-0782 that preferentially inhibited CDK2, CDK7 and CDK9 in the nanomolar range. The compound inhibited phosphorylation of CDK substrates and downregulated the short-lived proteins, Mcl-1 and cyclin D1. ICEC-0782 induced G2/M arrest and apoptosis. The permeability and cytotoxicity of ICEC-0782 were unaffected by ABC transporter expression. Following daily oral dosing, the compound inhibited growth of human colon HCT-116 and human breast MCF7 tumour xenografts in vivo by 84% and 94%, respectively.conclusion: We identified a promising pyrazolo[1,5-a]pyrimidine compound devoid of ABC transporter interaction, highly suitable for further preclinical and clinical evaluation for the treatment of cancer.

Journal article

Yang Y, Correa da Costa R, Fuchter MJ, Campbell AJet al., 2013, Circularly polarized light detection by a chiralorganic semiconductor transistor, Nature Photonics, Vol: 7, Pages: 634-638

Journal article

Yang Y, da Costa RC, Smilgies D-M, Campbell AJ, Fuchter MJet al., 2013, Induction of Circularly Polarized Electroluminescence from an Achiral Light-Emitting Polymer via a Chiral Small-Molecule Dopant, ADVANCED MATERIALS, Vol: 25, Pages: 2624-2628, ISSN: 0935-9648

Journal article

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