Research in our group is focused on utilising the power of organic chemistry, and developing new synthetic methods, to address problems of biochemical and medicinal significance. Projects are multidisciplinary in nature, involving a combination of solution- and solid-phase organic synthesis, flow-based technologies, computer-aided drug discovery, screening technologies and cutting edge in vitro and in vivo biology.
Novel vaccine development
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Under construction…
Papers
Hanna, C. C.; Ashhurst, A. S; Quan, D.; Maxwell, J. W. C.; Britton, W. J.; Payne, R. J. Synthetic protein conjugate vaccines provide protection against Mycobacterium tuberculosis in mice. Proc. Natl. Acad. Sci. U.S.A. 2021, 118 (4), e2013730118.
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Late-stage protein modification
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The modification of peptides and proteins has emerged as a powerful means to efficiently prepare high value bioconjugates for a range of applications in chemical biology and for the development of next-generation therapeutics. The importance of protein modifications in biology and the pharmaceutical/biotechnological industry has led to the search for new methods that can be used for efficient access to modified peptides and proteins in homogeneous form (either with PTMs or unnatural ‘designer’ modifications, e.g. PEGylation) from fully unprotected peptides and proteins.
In the Payne group we are interested in developing novel methodologies to accomplish the late‑stage modification of peptides and proteins. We are particularly interested in the targeting the amino acids cysteine and its congener, the 21st amino acid, selenocysteine.
Papers
Byrne, S.; Bedding, M.; Corcilius, L.; Ford, D.; Zhong, Y.; Franck, C.; Larance, M.; Mackay, J.; Payne, R. J. Late-stage modification of peptides and proteins at cysteine with diaryliodonium salts. Chem. Sci. 2021, 12, 14159-14166.
Mackay, A. S.; Payne, R. J.; Malins, L. R. Electrochemistry for the Chemoselective Modification of Peptides and Proteins. J. Am. Chem. Soc. 2022, 144(1), 23–41.
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De-novo discovery of macrocyclic peptides as next-generation therapeutics
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Under construction…
Papers
Johansen-Leete, J.; Ullrich, S.; Fry, S. E.; Frkic, R.; Bedding, M. J.; Aggarwal, A.; Ashhurst, A. S.; Ekanayake, K. B.; Mahawaththa, M. C.; Sasi, V. M.; Luedtke, S.; Ford, D. J.; O’Donoghue, A. J.; Passioura, T.; Larance, M.; Otting, G.; Turville, S.; Jackson, C. J.; Nitsche, C.; Payne, R. J. Antiviral Cyclic Peptides Targeting the Main Protease of SARS-CoV-2. Chem. Sci. 2022, DOI: 10.1039/D1SC06750Hx
Norman, A.; Franck, C.; Christie, M.; Hawkins, P. M. E.; Patel, K.; Ashhurst, A. S.; Aggarwal, A.; Low, J. K. K.; Siddiquee, R.; Ashley, C. L.; Steain, M.; Triccas, J. A.; Turville, S.; Mackay, J. P.; Passioura, T.; Payne, R. J. Discovery of Cyclic Peptide Ligands to the SARS-CoV-2 Spike Protein Using mRNA Display. ACS Cent. Sci. 2021, 7 (6), 1001-1008.
Ford, D. J.; Duggan, N. M.; Fry, S. E.; Ripoll-Rozada, J.; Agten, S. A.; Liu, W.; Corcilius, L.; Hackeng, T. M.; van Oerle, R.; Spronk, H. M. H.; Ashhurst, A. S.; Sasi, V. S.; Kaczmarski, J. A.; Jackson, C. J.; Pereira, P. J. B.; Passioura, T.; Suga, H.; Payne, R. J. Potent Cyclic Peptide Inhibitors of FXIIa Discovered by mRNA Display with Genetic Code Reprogramming. J. Med. Chem. 2021, 64 (11), 7853-7876.
Ford, D. J.; Duggan, N. M.; Fry, S. E.; Ripoll-Rozada, J.; Agten, S. A.; Liu, W.; Corcilius, L.; Hackeng, T. M.; van Oerle, R.; Spronk, H. M. H.; Ashhurst, A. S.; Sasi, V. S.; Kaczmarski, J. A.; Jackson, C. J.; Pereira, P. J. B.; Passioura, T.; Suga, H.; Payne, R. J. Potent Cyclic Peptide Inhibitors of FXIIa Discovered by mRNA Display with Genetic Code Reprogramming. J. Med. Chem. 2021, 64 (11), 7853-7876.
Johansen-Leete, J.; Passioura, T.; Foster, S.; Bhusal, R.; Ford, D.; Liu, M.; Jongkees, S.; Suga, H.; Stone, M. J.; Payne, R. J. Discovery of Potent Cyclic Sulfopeptide Chemokine Inhibitors via Reprogrammed Genetic Code mRNA Display. J. Am. Chem. Soc. 2020, 142 (20), 9141-9146
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Anti-infective drug development inspired by natural products
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Under construction…
Papers
Hawkins, P. M. E.; Hoi, D. M.; Cheung, C.-Y.; Wang, T.; Quan, D.; Sasi, V. M.; Liu, D. Y.; Linington, R. G.; Jackson, C. J.; Oehlers, S. H.; Cook, G. M.; Britton, W. J.; Clausen, T.; Payne, R. J. Potent Bactericidal Antimycobacterials Targeting the Chaperone ClpC1 Based on the Depsipeptide Natural Products Ecumicin and Ohmyungsamycin A. J. Med. Chem. 2022, DOI: 10.1021/acs.jmedchem.1c02122.
Tran, W.; Kusay, A. S.; Hawkins, P. M. E.; Cheung, C.Y.; Nagalingam, G.; Pujari, V.; Ford, D. J.; Stoye, A.; Ochoa, J. L.; Audette, R. E.; Hortle, E.; Oehlers, S. H.; Charman, S. A.; Linington, R. G.; Rubin, E. J.; Dowson, C. G.; Roper, D. I.; Crick, D. C.; Balle, T.; Cook, G. M.; Britton, W. J.; Payne, R. J. Synthetic Sansanmycin Analogues as Potent Mycobacterium tuberculosis Translocase I Inhibitors. J. Med. Chem. 2021. 64 (23), 17326–17345.
Ashhurst, A. S.; Tang, A. H.; Fajtová, P.; Yoon, M. C.; Aggarwal, A.; Bedding, M. J.; Stoye, A.; Beretta, L.; Pwee, D.; Drelich, A.; Skinner, D.; Li, L.; Meek, T. D.; McKerrow, J. H.; Hook, V.; Tseng, C.-T.; Larance, M.; Turville, S.; Gerwick, W. H.; O’Donoghue, A. J.; Payne, R. J. Potent Anti-SARS-CoV-2 Activity by the Natural Product Gallinamide A and Analogues via Inhibition of Cathepsin L. J. Med. Chem. 2021. DOI: 10.1021/acs.jmedchem.1c01494.
Hawkins, P.; Tran, W.; Nagalingam, G.; Cheung, C. Y.; Giltrap, A. M.; Cook, G.; Britton, W. J.; Payne, R. J. Total Synthesis and Antimycobacterial Activity of Ohmyungsamycin A, Deoxyecumicin, and Ecumicin. Chem. Eur. J. 2020. 26 (66), 15200-15205.
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Novel anti-coagulants from blood-feeding organisms
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Under construction…
Papers
Dowman, L. J.; Agten, S. M.; Ripoll-Rozada, J.; Calisto, B. M.; Pereira, P. J. B.; Payne, R. J. Synthesis and Evaluation of Peptidic Thrombin Inhibitors Bearing Acid-Stable Sulfotyrosine Analogues. Chem. Commun. 2021, 57, 10923-10926.
Agten, S. M.; Watson, E. E.; Ripoll-Rozada, J.; Dowman, L. J.; Wu, M. C. L.; Alwis, I.; Jackson, S. P.; Pereira, P. J. B.; Payne, R. J. Potent trivalent inhibitors of thrombin through hybridization of salivary sulfopeptides from hematophagous arthropods. Angew. Chem. Int. Ed. 2021, 60 (10), 5348-5356. *featured as a cover article and selected as a hot article
Clayton, D; Kulkarni, S. S.; Sayers, J.; Dowman, L. J.; Ripoll-Rozada, J.; Pereira, J. B. P.; Payne, R. J. Chemical synthesis of a haemathrin sulfoprotein library reveals enhanced thrombin inhibition following tyrosine sulfation. RSC Chem. Biol. 2020, 1, 379-384.
Watson, E. E.; Ripoll-Rozada, J.; Lee, A. C.; Wu, M. C, L.; Pasch, T.; Premdjee, B.; Franck, C.; Sayers, J.; Pinto, M. F.; Martins, P. M.; Jackson, S. P.; Pereira, P. J. B.;Payne, R. J. Rapid Assembly of a Library of Anticoagulant Sulfoproteins. Proc. Natl. Acad. Sci. U. S. A. 2019, 116 (28), 13873-13878.
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Novel strategies for peptide and protein synthesis
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Under construction…
Papers
Kulkarni, S.S.; Watson, E.E.; Maxwell, J.W.C.; Niederacher, G.; Johansen-Leete, J.; Huhmann, S.; Mukherjee, S.; Norman, A.R.; Kriegesmann, J.; Becker, C.F.W. and Payne, R.J. Expressed Protein Selenoester Ligation. Angew. Chem. Int. Ed. 2022, DOI: 10.1002/anie.202200163.
Kambanis, L.; Chisholm, T. S.; Kulkarni, S. S.; Payne, R. J. Rapid one-pot iterative diselenide-selenoester ligation using a novel coumarin-based photolabile protecting group. Chem. Sci. 2021, 12, 10014-10021.
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Discovery of novel anti-inflammatory agents
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Under construction…
Papers
Franck, C.; Foster, S. R.; Johansen-Leete, J.; Chowdhury, S.; Cielesh, M.; Bhusal, R. P.; Mackay, J. P.; Larance, M.; Stone, M. J.; Payne, R. J. Semisynthesis of an evasin from tick saliva reveals a critical role of tyrosine sulfation for chemokine binding and inhibition. Proc. Natl. Acad. Sci. U. S. A. 2020, 117 (23), 12657-12664.
Chisholm, T. S.; Kulkarni, S. S.; Hossain, K. R.; Cornelius, F.; Clarke, R. J.; Payne, R. J. Peptide Ligation at High Dilution via Reductive Diselenide-Selenoester Ligation. J. Am. Chem. Soc. 2020, 142 (2), 1090-1100.
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Payne Research Group 