Flor A. Gowans, Danny Q. Thach, Zhouyang Zhu, Yangzhi Wang, Belen E. Altamirano Poblano, Dustin Dovala, John A. Tallarico, Jeffrey M. McKenna, Markus Schirle, Thomas J. Maimone, and Daniel K. Nomura
A blog highlighting recent publications in the area of covalent modification of proteins, particularly relating to covalent-modifier drugs. @CovalentMod on Twitter, @covalentmod@mstdn.science on Mastodon, and @covalentmod.bsky.social on BlueSky
Monday, May 13, 2024
Ophiobolin A Covalently Targets Mitochondrial Complex IV Leading to Metabolic Collapse in Cancer Cells
Thursday, May 9, 2024
Discovery and Preclinical Characterization of BIIB129, a Covalent, Selective, and Brain-Penetrant BTK Inhibitor for the Treatment of Multiple Sclerosis
Martin K. Himmelbauer, Bekim Bajrami, Rebecca Basile, Andrew Capacci, TeYu Chen, Colin K. Choi, Rab Gilfillan, Felix Gonzalez-Lopez de Turiso, Chungang Gu, Marc Hoemberger, Douglas S. Johnson, J. Howard Jones, Ekta Kadakia, Melissa Kirkland, Edward Y. Lin, Ying Liu, Bin Ma, Tom Magee, Srinivasa Mantena, Isaac E. Marx, Claire M. Metrick, Michael Mingueneau, Paramasivam Murugan, Cathy A. Muste, Prasad Nadella, Marta Nevalainen, Chelsea R. Parker Harp, Vatee Pattaropong, Alicia Pietrasiewicz, Robin J. Prince, Thomas J. Purgett, Joseph C. Santoro, Jurgen Schulz, Simone Sciabola, Hao Tang, H. George Vandeveer, Ti Wang, Zain Yousaf, Christopher J. Helal, and Brian T. Hopkins
Sunday, May 5, 2024
Histidine-Covalent Stapled Alpha-Helical Peptides Targeting hMcl-1
Giulia Alboreggia, Parima Udompholkul, Carlo Baggio, Kendall Muzzarelli, Zahra Assar, and Maurizio Pellecchia
Journal of Medicinal Chemistry 2024
DOI: 10.1021/acs.jmedchem.4c00277
Several novel and effective cysteine targeting (Cys) covalent drugs are in clinical use. However, the target area containing a druggable Cys residue is limited. Therefore, methods for creating covalent drugs that target different residues are being looked for; examples of such ligands include those that target the residues lysine (Lys) and tyrosine (Tyr). Though the histidine (His) side chain is more frequently found in protein binding locations and has higher desirable nucleophilicity, surprisingly limited research has been done to specifically target this residue, and there are not many examples of His-targeting ligands that have been rationally designed. In the current work, we created novel stapled peptides that are intended to target hMcl-1 His 252 covalently. We describe the in vitro (biochemical, NMR, and X-ray) and cellular design and characterization of such agents. Our findings further suggest that the use of electrophiles to specifically target His residues is warranted.
Ophiobolin A Covalently Targets Mitochondrial Complex IV Leading to Metabolic Collapse in Cancer Cells
Flor A. Gowans, Danny Q. Thach, Zhouyang Zhu, Yangzhi Wang, Belen E. Altamirano Poblano, Dustin Dovala, John A. Tallarico, Jeffrey M. McKe...
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Linqi Cheng Yixian Wang, Yiming Guo, Sophie S. Zhang Han Xiao C ell Chemical Biology, 2024 Volume 31, 3, 428 - 445 https://doi.org/10.10...
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Cravatt, B.; Njomen, E.; Hayward, R.; DeMeester, K.; Ogasawara, D.; Dix, M.; Nguyen, T.; Ashby, P.; Simon, G.; Schreiber, S.; Melillo, B. C...
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Grob, N. M.; Remarcik, C.; Rössler, S. L.; Wong, J. Y. K.; Wang, J. C. K.; Tao, J.; Smith, C. L.; Loas, A.; Buchwald, S. L.; Eaton, D. L.; P...