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Optimization of the Biological Activity of Combinatorial Compound Libraries by a Genetic Algorithm
Author(s) -
Weber Lutz,
Wallbaum Sabine,
Broger Clemens,
Gubernator Klaus
Publication year - 1995
Publication title -
angewandte chemie international edition in english
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 0570-0833
DOI - 10.1002/anie.199522801
Subject(s) - combinatorial chemistry , thrombin , enzyme , biological activity , function (biology) , active site , chemistry , thrombin generation , biochemistry , biology , in vitro , genetics , immunology , platelet
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 ( K i = 0.22 μM).