A journey in structure-based drug discovery: From designed peptides to protein surface topomimetics as antibiotic and antiangiogenic agents

Ruud P.M. Dings, Kevin H. Mayo

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Most biological events are mediated through molecular interactions by proteins, and because proteins are composed of structural units like helices, β-sheets and turns, small peptides and peptidomimetics may be used to mimic their biological effects and even as therapeutic agents in the clinic. Here, we present a structure-based, scaffold-driven approach to design bioactive peptides and peptidomimetics. Initially, we designed a novel series of β-sheet-forming peptides that mimic the activities of both antibiotic bacterial membrane disrupting peptides and antiangiogenic proteins. We subsequently used structure-activity relationships to reduce the design to partial peptide mimetics and then to fully nonpeptide topomimetics. Some of these agents are currently in extensive preclinical studies for further development as drug candidates against infectious disease and cancer.

Original languageEnglish (US)
Pages (from-to)1057-1065
Number of pages9
JournalAccounts of Chemical Research
Volume40
Issue number10
DOIs
StatePublished - Oct 2007

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