A platform for in-solution enrichment from large libraries to identify peptide inhibitors of protein-protein interactions

A platform for in-solution enrichment from large libraries to identify peptide inhibitors of protein-protein interactions

A platform for in-solution enrichment from large libraries to identify peptide inhibitors of protein-protein interactions (#26)

Bradley L Pentelute ¹

MIT, Cambridge, MA, United States

Here we report a platform for improving the affinity of peptide-based inhibitors of protein-protein interactions using non-canonical amino acids. With this platform—which is inherently selective for high-affinity binders—we realized up to ~100 or ~30-fold gains in affinity for binders to the oncogenic ubiquitin ligase MDM2 or the HIV capsid protein C-terminal domain (C-CA). We demonstrated the utility of the identified compounds as functional PPI inhibitors by rendering them cell permeable via macrocyclization to target MDM2 in cancer cells.

Authors contributing to this presentation.

Pentelute, B.L

Bradley L. Pentelute, Associate Professor of Chemistry. He is also an Associate Member, Broad Institute of Harvard and MIT, an Extramural Member of the MIT Koch Cancer Institute, and Member, Center for Environmental Health Sciences MIT. He received his undergraduate degree in Psychology and Chemistry from the University of Southern California, and his M.S and Ph.D. in Organic Chemistry from the University of Chicago with Prof. Steve Kent. He was a postdoctoral fellow in the laboratory of Dr. R. John Collier at Harvard Medical School, Microbiology.

A platform for in-solution enrichment from large libraries to identify peptide inhibitors of protein-protein interactions (#26)

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Pentelute, B.L

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