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De Novo Design, Synthesis, and In Vitro Evaluation of a New Class of Nonpeptidic Inhibitors of the Malarial Enzyme Plasmepsin II
Author(s) -
Carcache David A.,
Hörtner Simone R.,
Bertogg Andreas,
Binkert Christoph,
Bur Daniel,
Märki Hans Peter,
Dorn Arnulf,
Diederich François
Publication year - 2002
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/1439-7633(20021104)3:11<1137::aid-cbic1137>3.0.co;2-a
Subject(s) - stereochemistry , enzyme , chemistry , computational biology , in vitro , biochemistry , combinatorial chemistry , biology
Pocket change : A new family of plasmepsin II inhibitors (see scheme) was developed by taking advantage of the putative flexibility of plasmepsin II and employment of a structure‐based de novo design approach based on molecular recognition principles. A newly accessible hydrophobic pocket unlocked by conformational changes that occur upon bonding of adequate inhibitors was proposed. This site was targeted by nonpeptidic plasmepsin II inhibitors, which displayed single‐digit micromolar activity in an enzyme assay.