(Graph Presented) 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.
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