Genetically Selected Cyclic‐Peptide Inhibitors of AICAR Transformylase Homodimerization

Abstract

Finding the needle in a haystack need not be as troublesome as once thought. By coupling disruption of protein–protein (X–X) interactions to host-cell survival (see figure), inhibitors of ATIC (a key enzyme in the de novo purine biosynthetic pathway) were readily identified from a biosynthesized library of 107 small molecules. The activity and selectivity of nine cyclic peptides selected by this method were demonstrated in vivo and in vitro. AICAR=aminoimidazole-4-carboxamide ribonucleotide. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2005/z500417_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.