John E. Moses

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John E. Moses
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Born (1975-01-10) January 10, 1975 (age 49)
NationalityWelsh, British
Alma materUniversity of Bath
University of Oxford
Known forClick Chemistry, Biomimetic Synthesis and Organic Chemistry
Awards2021 Royal Society of Chemistry Organic Division Horizon Prize: Robert Robinson Award in Synthetic Organic Chemistry

John Edward Moses (born January 10, 1975) is a Welsh organic chemist and is currently Professor of Click Chemistry at Cold Spring Harbor Laboratory (CSHL). In 2020, he established the first synthetic organic chemistry research group at CSHL, where he leads the click chemistry research group and Chemistry for Biology program.[1][2] He is a member of the CSHL Cancer Center (NCI designated). He is known for his work on the development and application of Click Chemistry and Biomimetic Synthesis.

Education and Training

Originally from Rhosllanerchrugog, Wrexham, North Wales, Moses graduated with a degree in Chemistry from the University of Bath, having spent one year at Purdue University. Thereafter, he undertook a DPhil in the Biomimetic Synthesis of Complex Natural Products under Professor Sir Jack Baldwin, FRS, at the University of Oxford. In 2004, he moved to The Scripps Research Institute, La Jolla (USA), to work with Nobel laureate Professor K. B. Sharpless on the development of click chemistry.

Career

In 2005, Moses was awarded a RCUK-EPSRC Fellowship in Cancer Medicinal Chemistry and took up a position at the School of Pharmacy, University College London. In September 2007, he was appointed Associate Professor in Organic Chemistry at the University of Nottingham and was promoted to Reader and Associate Professor in 2011. In 2017, he moved to Australia to take up the position of Chair of Organic Chemistry at La Trobe Institute for Molecular Science. Moses joined Cold Spring Harbor Laboratory (CSHL) in September 2020,[3] as CSHL’s first Professor of Click Chemistry. The Click Chemistry Laboratory occupies a state-of-the-art chemistry laboratory in the newly refurbished Demerec building.

In addition to his own research activities, Moses has spent significant time helping to build institutes in the developing world. In 2011, he was appointed as a Distinguished Visiting Professor at King Saud University, Saudi Arabia, where he mentored scientists at the female college of chemistry. In 2012, Moses helped to establish the “Amity Institute for Click Chemistry Research and Studies (AICCRS),” at Amity University, India.[4] He is currently the honorary Chairman of AICCRS.[5]

Research

Moses has spent his independent research career developing new click chemistry reactions and biomimetic strategies for complex natural product synthesis. His group exploits these technologies to discover functional molecules, such as chemical probes, materials, and drug-like biologically active molecules.

During his time at the School of Pharmacy, University College London, he pioneered the application of Click Chemistry in anticancer drug discovery, developing the first therapeutic DNA binding 1,2,3-triazole ligands that interact selectively with the G-quadruplex regions of the telomere.[6][7] These ligands demonstrate significant selectivity for quadruplex structures over duplex DNA. Moses later developed the first fragment-based Click Chemistry approach synthesis of inhibitors of lactate dehydrogenase-5 (LDH5),[8]an essential metabolic enzyme that is crucial for the survival of tumor cells, particularly those in an oxygen-starved environment known as the Warburg effect. Additionally, Moses has combined his expertise in Biomimetic Synthesis and Click Chemistry in other ways, leading to the discovery of several potent anticancer and antibiotic agents.[9][10][11][12]

Since 2016, Moses has helped to develop a new click reaction class called Sulfur-Fluoride Exchange (SuFEx). He has established several new click reactions, including SuFEx mediated synthesis of hindered amides,[13] multidimensional click chemistry[14] and late-stage SuFEx synthesis of fluorinated ligands. In 2020, Moses reported a new method for drug discovery named Diversity Oriented Clicking (DOC).[15] DOC exploits a combination of classical “Click” transformations with distinct SuFEx hubs (e.g., SASFs), enabling the rapid synthesis of structurally diverse molecular libraries for biological screening. The DOC method has led to the discovery of two new drug classes, including a potent antibiotic that overcomes bacterial resistance mechanisms and a new family of microtubule-disrupting anticancer agents that are effective against aggressive and otherwise drug-resistant cancer cell lines. In 2022, Moses and his team established an improved SuFEx protocol, coined Accelerated SuFEx Click Chemistry (ASCC),[16] which allows rapid lead discovery and drug analog optimization. Moses’ laboratory collaborates with several teams worldwide (UK, China, Australia), including several colleagues at CSHL.

In addition, Moses has served as a research mentor of over 20 graduate students for their Ph.D. dissertation and more than 22 postdoctoral researchers at five educational institutes (UK, Australia, USA), including, since September 2020, Cold Spring Harbor Laboratory.

Professional Memberships, Honors, and Awards

Professional Memberships

2021 – Present Member, American Association for Cancer Research (AACR)
2015 – 2015 Fellow, Royal Society of Chemistry (RSC)
1997 – 2015 Member, Royal Society of Chemistry (RSC)
2000 – Present Member, American Chemical Society (ACS).

Honors and Awards

2021 Royal Society of Chemistry 2021 Organic Division Horizon Prize: Robert Robinson Award in Synthetic Organic Chemistry
2020 Foreign 1000 talent plan, Chinese Central Government (declined)
2017–2021 Australian Research Council Future Fellowship
2015 Fellow of the Royal Society of Chemistry (FRSC)
2012 Honorary Chairman and Professor, Amity University, Noida, India
2011 Distinguished Visiting Professor, King Saud University, Riyadh, Saudi Arabia
2011 Thieme Chemistry Journal Award 2011
2010 United Kingdom & Republic of Ireland Lilly Award for Excellence in Organic Chemistry
2005 United Kingdom Research Councils Early Career Fellowship

Major Publications

  • Moorhouse AD, Santos AM, Gunaratnam M, Moore M, Neidle S, Moses JE. Stabilization of G-quadruplex DNA by highly selective ligands via click chemistry. J Am Chem Soc. 2006 Dec 20;128(50):15972-3. doi: 10.1021/ja0661919. PMID: 17165715.
  • Moorhouse AD, Haider S, Gunaratnam M, Munnur D, Neidle S, Moses JE. Targeting telomerase and telomeres: a click chemistry approach towards highly selective G-quadruplex ligands. Mol Biosyst. 2008 Jun;4(6):629-42. doi: 10.1039/b801822g. Epub 2008 Apr 8. PMID: 18493662.
  • Lombardo CM, Martínez IS, Haider S, Gabelica V, De Pauw E, Moses JE, Neidle S. Structure-based design of selective high-affinity telomeric quadruplex-binding ligands. Chem Commun (Camb). 2010 Dec 28;46(48):9116-8. doi: 10.1039/c0cc02917c. Epub 2010 Oct 29. PMID: 21038041.
  • Li S, Li G, Gao B, Pujari SP, Chen X, Kim H, Zhou F, Klivansky LM, Liu Y, Driss H, Liang DD, Lu J, Wu P, Zuilhof H, Moses J, Sharpless KB. SuFExable polymers with helical structures derived from thionyl tetrafluoride. Nat Chem. 2021 Sep;13(9):858-867. doi: 10.1038/s41557-021-00726-x. Epub 2021 Aug 16. PMID: 34400816.
  • Manzi L, Barrow AS, Scott D, Layfield R, Wright TG, Moses JE, Oldham NJ. Carbene footprinting accurately maps binding sites in protein-ligand and protein-protein interactions. Nat Commun. 2016 Nov 16;7:13288. doi: 10.1038/ncomms13288. PMID: 27848959.
  • Manzi L, Barrow AS, Hopper JTS, Kaminska R, Kleanthous C, Robinson CV, Moses JE, Oldham NJ. Carbene Footprinting Reveals Binding Interfaces of a Multimeric Membrane-Spanning Protein. Angew Chem Int Ed Engl. 2017 Nov 20;56(47):14873-14877. doi: 10.1002/anie.201708254. Epub 2017 Oct 20. PMID: 28960650.
  • Jenner M, Kosol S, Griffiths D, Prasongpholchai P, Manzi L, Barrow AS, Moses JE, Oldham NJ, Lewandowski JR, Challis GL. Mechanism of intersubunit ketosynthase-dehydratase interaction in polyketide synthases. Nat Chem Biol. 2018 Mar;14(3):270-275. doi: 10.1038/nchembio.2549. Epub 2018 Jan 8. PMID: 29309054.

References

  1. ↑ "Cold Spring Harbor Opens First Ever Chemistry Lab". 10 November 2020.
  2. ↑ "Cold Spring Harbor Laboratory to open first chemistry lab in its 130-year history".
  3. ↑ "Combining chemistry and biology at CSHL". October 2020.
  4. ↑ "Amity Institute of Click Chemistry Research and Studies: About Us".
  5. ↑ "Amity Institute of Click Chemistry Research and Studies: Faculty".
  6. ↑ Moorhouse, Adam D.; Santos, Ana Mafalda; Gunaratnam, Mekala; Moore, Michael; Neidle, Stephen; Moses, John E. (2006-12-01). "Stabilization of G-Quadruplex DNA by Highly Selective Ligands via Click Chemistry". Journal of the American Chemical Society. 128 (50): 15972–15973. doi:10.1021/ja0661919. ISSN 0002-7863. PMID 17165715.
  7. ↑ Moorhouse, Adam D.; Haider, Shozeb; Gunaratnam, Mekala; Munnur, Deeksha; Neidle, Stephen; Moses, John E. (2008). "Targeting telomerase and telomeres: a click chemistry approach towards highly selective G-quadruplex ligands". Molecular BioSystems. 4 (6): 629–642. doi:10.1039/b801822g. ISSN 1742-206X. PMID 18493662.
  8. ↑ Moorhouse, Adam D.; Spiteri, Christian; Sharma, Pallavi; Zloh, Mire; Moses, John E. (2011). "Targeting glycolysis: a fragment based approach towards bifunctional inhibitors of hLDH-5". Chem. Commun. 47 (1): 230–232. doi:10.1039/c0cc01166e. ISSN 1359-7345. PMID 20676418.
  9. ↑ Silverman, Steven M.; Moses, John E.; Sharpless, K. Barry (2016-11-11). "Reengineering Antibiotics to Combat Bacterial Resistance: Click Chemistry [1,2,3]-Triazole Vancomycin Dimers with Potent Activity against MRSA and VRE". Chemistry - A European Journal. 23 (1): 79–83. doi:10.1002/chem.201604765. ISSN 0947-6539. PMID 27747932.
  10. ↑ Han, Li-Chen; Stanley, Paul A.; Wood, Paul J.; Sharma, Pallavi; Kuruppu, Anchala I.; Bradshaw, Tracey D.; Moses, John E. (2016). "Horner–Wadsworth–Emmons approach to piperlongumine analogues with potent anti-cancer activity". Organic & Biomolecular Chemistry. 14 (31): 7585–7593. doi:10.1039/c6ob01160h. ISSN 1477-0520. PMID 27443386.
  11. ↑ "New shape-shifting antibiotics could fight deadly infections". 4 April 2023.
  12. ↑ "A new, sustainable source for a promising cancer killer". 23 March 2023.
  13. ↑ Smedley, Christopher J.; Barrow, Andrew S.; Spiteri, Christian; Giel, Marie-Claire; Sharma, Pallavi; Moses, John E. (2017-07-26). "Sulfur-Fluoride Exchange (SuFEx)-Mediated Synthesis of Sterically Hindered and Electron-Deficient Secondary and Tertiary Amides via Acyl Fluoride Intermediates". Chemistry - A European Journal. 23 (42): 9990–9995. doi:10.1002/chem.201701552. ISSN 0947-6539. PMID 28612408.
  14. ↑ Li, Suhua; Wu, Peng; Moses, John E.; Sharpless, K. Barry (2017-03-06). "Multidimensional SuFEx Click Chemistry: Sequential Sulfur(VI) Fluoride Exchange Connections of Diverse Modules Launched From An SOF 4 Hub". Angewandte Chemie International Edition. 56 (11): 2903–2908. doi:10.1002/anie.201611048. PMC 5434761. PMID 28165188.
  15. ↑ Smedley, Christopher J.; Li, Gencheng; Barrow, Andrew S.; Gialelis, Timothy L.; Giel, Marie‐Claire; Ottonello, Alessandra; Cheng, Yunfei; Kitamura, Seiya; Wolan, Dennis W.; Sharpless, K. Barry; Moses, John E. (2020-07-20). "Diversity Oriented Clicking (DOC): Divergent Synthesis of SuFExable Pharmacophores from 2‐Substituted‐Alkynyl‐1‐Sulfonyl Fluoride (SASF) Hubs". Angewandte Chemie International Edition. 59 (30): 12460–12469. doi:10.1002/anie.202003219. ISSN 1433-7851. PMC 7572632. PMID 32301265.
  16. ↑ Smedley, Christopher J.; Homer, Joshua A.; Gialelis, Timothy L.; Barrow, Andrew S.; Koelln, Rebecca A.; Moses, John E. (2021-12-07). "Accelerated SuFEx Click Chemistry For Modular Synthesis**". Angewandte Chemie International Edition. 61 (4): e202112375. doi:10.1002/anie.202112375. ISSN 1433-7851. PMC 8867595. PMID 34755436.

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