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John Moses

John E. Moses

Professor
Cancer Center Member

Ph.D. (DPhil), University of Oxford, 2004

moses@cshl.edu | 516-367-5560

Moses Lab Website   Faculty Profile

My group uses click chemistry to study biological systems at the molecular level. We develop and exploit powerful bond-forming click reactions that enable the rapid synthesis of small functional molecules, including cancer drugs and chemical probes. We apply these novel molecular tools in multidisciplinary discovery projects spanning the fields of biology and chemistry.

John Moses’ lab specializes in click chemistry, a powerful discovery method that relies upon the most robust chemical reactions to synthesize functional molecules. Small molecules are important because Nature’s machinery, including proteins, enzymes, and receptors, evolved to interact selectively with molecular ligands, similar to how a key fits a lock.

Using click chemistry, we create molecular probes for studying biological systems that may lead to new treatments for deadly diseases, including cancer. For example, we developed a new class of therapeutic DNA binding ligand that interacts selectively with telomeric regions of the genome involved in cellular maintenance. Several of these telomere binding ligands show remarkable selectivity and potency against cancer cells and tumours.

Further developing click chemistry, we recently described a discovery method called Diversity Oriented Clicking, which exploits a focussed group of reliable click chemistry reactions to achieve structural diversity. Our Diversity-Clicking approach led to the discovery of a new group of antibiotics with activity against multidrug-resistant bacteria, including MRSA.

Through the application of click chemistry, the Moses group is committed to developing Chemistry For Biology at Cold Spring Harbor Laboratory.

Winner: 2021 Organic Division Horizon Prize: Robert Robinson Award in Synthetic Organic Chemistry
Member of the American Chemical Society; 2019
Chartered Member of the Royal Australian Chemical Institute (MRACI CChem); 2018
Fellow of Royal Society of Chemistry (FRSC); 2015
Thieme Chemistry Award; 2011
UK & ROI Lilly Award: Excellence in Organic Chemistry; 2011
King Saud University, Award; 2011
William Boland Award; University of Bath; 2001

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All Publications

Diversity oriented clicking delivers β-substituted alkenyl sulfonyl fluorides as covalent human neutrophil elastase inhibitors

13 Sep 2022 | Proceedings of the National Academy of Sciences of USA | 119(37):e2208540119
Cheng, Yunfei, Li, Gencheng, Smedley, Christopher, Giel, Marie-Claire, Kitamura, Seiya, Woehl, Jordan, Bianco, Giulia, Forli, Stefano, Homer, Joshua, Cappiello, John, Wolan, Dennis, Moses, John, Sharpless, K

Shapeshifting Antibiotics: Bullvalene Linked Vancomycin Dimers are Effective Against Multidrug-Resistant Gram-Positive Bacteria

21 Apr 2022 | American Chemical Society (ACS)
Ottonello, Alessandra, Wyllie, Jessica, Yahiaoui, Oussama, Murray, Ewan, Williams, Paul, Bolla, Jani, Robinson, Carol, Fallon, Thomas, Soares da Costa, Tatiana, Moses, John

Accelerated SuFEx Click Chemistry For Modular Synthesis

9 Nov 2021 | Angewandte Chemie International Edition
Smedley, Christopher, Homer, Joshua, Gialelis, Timothy, Barrow, Andrew, Koelln, Rebecca, Moses, John

SuFExable polymers with helical structures derived from thionyl tetrafluoride.

16 Aug 2021 | Nature Chemistry
Li, Suhua, Li, Gencheng, Gao, Bing, Pujari, Sidharam, Chen, Xiaoyan, Kim, Hyunseok, Zhou, Feng, Klivansky, Liana, Liu, Yi, Driss, Hafedh, Liang, Dong-Dong, Lu, Jianmei, Wu, Peng, Zuilhof, Han, Moses, John, Sharpless, K

Aminium cation-radical catalysed selective hydration of (E)-aryl enynes.

22 Jun 2021 | Chemical Communications
Giel, Marie-Claire, Barrow, Andrew, Smedley, Christopher, Lewis, William, Moses, John

Accelerated SuFEx Click Chemistry for Modular Synthesis

25 Jan 2021 | ChemRxiv
Smedley, Christopher, Gialelis, Timothy, Moses, John

Frontispiz: Diversity Oriented Clicking (DOC): Divergent Synthesis of SuFExable Pharmacophores from 2-Substituted-Alkynyl-1-Sulfonyl Fluoride (SASF) Hubs

20 Jul 2020 | Angewandte Chemie International Edition | 132(30)
Smedley, C, Li, G, Barrow, A, Gialelis, T, Giel, M, Ottonello, A, Cheng, Y, Kitamura, S, Wolan, D, Sharpless, K, Moses, J

Diversity Oriented Clicking (DOC): Divergent Synthesis of SuFExable Pharmacophores from 2-Substituted-Alkynyl-1-Sulfonyl Fluoride (SASF) Hubs

20 Jul 2020 | Angewandte Chemie International Edition | 132(30):12560-12569
Smedley, C, Li, G, Barrow, A, Gialelis, T, Giel, M, Ottonello, A, Cheng, Y, Kitamura, S, Wolan, D, Sharpless, K, Moses, J

Diversity Oriented Clicking (DOC): Divergent Synthesis of SuFExable Pharmacophores from 2-Substituted-Alkynyl-1-Sulfonyl Fluoride (SASF) Hubs

16 Apr 2020 | Angewandte Chemie International Edition
Smedley, C, Li, G, Barrow, A, Gialelis, T, Giel, M, Ottonello, A, Cheng, Y, Kitamura, S, Wolan, D, Sharpless, K, Moses, J

Metal-Free Synthesis of Functional 1-Substituted-1,2,3-Triazoles from Ethenesulfonyl Fluoride and Organic Azides

13 Jan 2020 | Angewandte Chemie International Edition | 59(3):1181-1186
Giel, M, Smedley, C, Mackie, E, Guo, T, Dong, J, Soares da Costa, T, Moses, J

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