Metallopeptides — from Drug Discovery to Catalysis

Authors


  • This review is a result of a lectureship sponsored by the Chemistry Research Promotion Center of the National Science Council of Taiwan, May 15-May 22, 2009 (hosted by Prof. Yaw-Kuen Li). Lectures on this topic were delivered at the National Dong Hua University and the National Chiao Tung University. Our research on metallopeptides has been supported by the National Science Foundation (CHE-0718625).

Abstract

Oligopeptides are involved in diverse biological activities, including neurotransmission and antibiotic. Many natural-occurring peptides and peptide-ketide hybrids exhibit specific biological activities and chemical reactivities upon binding with certain metal ions, such as divalent metal-binding antibiotic bacitracin and anticancer Fe/Cu-bleomycin. There are also numerous synthetic peptides designed to bind metal ions to exhibit wide range of physical properties and chemical and biological activities. In this review we summarize the background and discuss our research on metal binding properties, structures, and chemical reactivities of three metallopeptides, the bacterial antibiotic bacitracin, the Alzheimer's disease-related β-amyloid, and the salivary antimicrobial histatin. Despite their different structures and biological functions, the Cu2+ complexes of these peptides exhibit significant activities toward catechol oxidation and phenol hydroxylation. However, the mechanisms of the oxidative reactions among these three Cu-peptides seem to be distinctively different. Our current understanding about the structure-bioactivity relationship and chemical reactivities as well as implications in drug discovery of these peptides are summarized herein.

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