Open AccessNon-Covalent Inhibitors of the 20S Proteasome
Author(s) -
Carlos GarcíaEcheverría,
Patricia Imbach,
Johannes Roesel,
Peter G. Fuerst,
Marc Lang,
Vito Guagnano,
Maria Noorani,
Johann Zimmermann,
Pascal Furet
Publication year - 2003
Publication title -
chimia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.387
H-Index - 55
eISSN - 2673-2424
pISSN - 0009-4293
DOI - 10.2533/000942903777679415
Subject(s) - peptidomimetic , proteasome , covalent bond , chemistry , protease , potency , enzyme , in vitro , biochemistry , structure–activity relationship , combinatorial chemistry , stereochemistry , peptide , organic chemistry
Peptidomimetics have been commonly used as lead compounds to design inhibitors with high affinity and specificity for a particular enzyme. The discovery that a 2-aminobenzylstatine derivative originally designed to target an aspartyl protease was able to inhibit specifically and non-covalently the chymotrypsin-like activity of the 20S proteasome represented a unique starting point for our medicinal chemistry endeavor for this target. Utilizing a structure-based design approach, we have been able to improve the potency of this new class of proteasome inhibitors without affecting its in vitro selectivity profile.