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Peptoid Cancer Drugs Targeting PCNA Designed via a Novel in Silico/In Vitro Discovery Pipeline

总结

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.

技术优势

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

技术应用

Drug discovery Cancer therapy

详细技术说明

V. Jo DavissonPurdue Medicinal Chemistry and Molecular Pharmacology

*Abstract

*Background

Fragment-based drug discovery is a popular method used to design molecules that bind to protein targets. In this method, many small compounds are screened for their binding to a target protein. Subsequently, steps are undertaken to combine more than one of the small compounds found to bind weakly into a larger, stronger-binding, drug-like compound. Fragment-based drug discovery presents a significant challenge; information must be known about the binding sites of the fragments so that they can be combined in a way that does not disrupt the binding of the individual fragments. In addition, many important drug target proteins participate in protein-protein interactions. Disrupting such interactions is critical to disrupting the chemical signals that drive cancer and other diseases.

*IP Issue Date

None

*IP Type

Provisional

*Stage of Development

Proof of concept

*Web Links

Purdue Office of Technology CommercializationPurdueInnovation and EntrepreneurshipV. Jo DavissonPurdue Medicinal Chemistry and Molecular Pharmacology

国家

United States

申请号码

None

国家/地区

美国