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Genetically Selected Cyclic‐Peptide Inhibitors of AICAR Transformylase Homodimerization
Author(s) -
Tavassoli Ali,
Benkovic Stephen J.
Publication year - 2005
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.200500417
Subject(s) - haystack , in vitro , enzyme , peptide , chemistry , biochemistry , purine , biology , computational biology , computer science , world wide web
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 10 7 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.