Optimization of the Biological Activity of Combinatorial Compound Libraries by a Genetic Algorithm

Abstract

Artificial evolutionary synthesis can be used to find biologically active compounds out of a library of 160000 possible Ugi-type reaction products by using an enzymatic assay (thrombin) as the feedback loop function. Thus, a reaction in generation 18 gave compound 1, which exhibits the structural features of known thrombin inhibitors and inhibits the enzyme effectively (Ki = 0.22 μM).