Peptoid Cancer Drugs Targeting PCNA Designed via a Novel in Silico/In Vitro Discovery Pipeline
To overcome the challenges of traditional fragment-based drug design, researchers at Purdue University used a combination of computational and experimental technique to discover novel inhibitors of the interaction between proliferating cell nuclear antigen (PCNA) and a peptide that binds to a site on PCNA responsible for multiple protein-protein interactions relevant to its cellular function. Specifically, thousands of tripeptoids (peptide-like molecules with three chemically distinct sites) were screened in silico, facilitating the selection of a small number of tripeptoids for in vitro testing. Several of the selected tripeptoids show a good ability to disrupt the PCNA-peptide interaction. This method of drug discovery successfully identified a small number of hit compounds that disrupt a protein-protein interaction involving PCNA, an important cancer target.
Potential first-in-class cancer drug Fewer compounds synthesized Less structural information needed than in traditional fragment-based drug discovery Well-suited to targeting protein-protein interactions
Drug discovery Cancer therapy
V. Jo DavissonPurdue Medicinal Chemistry and Molecular Pharmacology
United States
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美國
