John Moses

John E. Moses

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

Protocol for producing phosphoramidate using phosphorus fluoride exchange click chemistry

12 Jan 2024 | STAR Protocols | 5(1):102824
Homer, Joshua, Sun, Shoujun, Koelln, Rebecca, Moses, John

Sulfur fluoride exchange

1 Dec 2023 | Nature Reviews Methods Primers | 3(1)
Homer, J, Xu, L, Kayambu, N, Zheng, Q, Choi, E, Kim, B, Sharpless, K, Zuilhof, H, Dong, J, Moses, J

The certainty of a few good reactions

10 Aug 2023 | Chem | 9(8):2063-2077
Moorhouse, A, Homer, J, Moses, J

Phosphorus fluoride exchange: Multidimensional catalytic click chemistry from phosphorus connective hubs

10 Aug 2023 | Chem | 9(8):2128-2143
Sun, S, Homer, J, Smedley, C, Cheng, Q, Sharpless, K, Moses, J

Ethene-1,1-disulfonyl Difluoride (EDSF) for SuFEx Click Chemistry: Synthesis of SuFExable 1,1-Bissulfonylfluoride Substituted Cyclobutene Hubs

24 Jul 2023 | Angewandte Chemie International Edition | 62(30):e202303916
Smedley, Christopher, Giel, Marie-Claire, Fallon, Thomas, Moses, John

Inhibition of mitochondrial metabolism by (-)-jerantinine A: synthesis and biological studies in triple-negative breast cancer cells

26 Apr 2023 | RSC Medicinal Chemistry | 14(4):710-714
Gialelis, Timothy, Wang, Zifei, Homer, Joshua, Yang, Wen-Hsuan, Chung, Taemoon, Hu, Qingting, Smedley, Christopher, Pawar, Nitin, Upadhyay, Nitinkumar, Tuveson, David, Lyons, Scott, Lukey, Michael, Moses, John

Shapeshifting bullvalene-linked vancomycin dimers as effective antibiotics against multidrug-resistant gram-positive bacteria.

11 Apr 2023 | Proceedings of the National Academy of Sciences of the United States of America | 120(15):e2208737120
Ottonello, Alessandra, Wyllie, Jessica, Yahiaoui, Oussama, Sun, Shoujun, Koelln, Rebecca, Homer, Joshua, Johnson, Robert, Murray, Ewan, Williams, Paul, Bolla, Jani, Robinson, Carol, Fallon, Thomas, Soares da Costa, Tatiana, Moses, John

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 the United States of America | 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
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

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