期刊
ACCOUNTS OF CHEMICAL RESEARCH
卷 40, 期 10, 页码 1057-1065出版社
AMER CHEMICAL SOC
DOI: 10.1021/ar700086k
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资金
- NCI NIH HHS [CA096090] Funding Source: Medline
- NIAID NIH HHS [AI057153] Funding Source: Medline
Most biological events are mediated through molecular interactions by proteins, and because proteins are composed of structural units like helices, beta-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 structurebased, scaffold-driven approach to design bioactive peptides and peptidomimetics. Initially, we designed a novel series of fi-sheetforming 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.
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