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Probing the Bioactive Conformation of an Archetypal Natural Product HDAC Inhibitor with Conformationally Homogeneous Triazole‐Modified Cyclic Tetrapeptides
Author(s) -
Horne W. Seth,
Olsen Christian A.,
Beierle John M.,
Montero Ana,
Ghadiri M. Reza
Publication year - 2009
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.200805900
Subject(s) - tetrapeptide , chemistry , peptide bond , stereochemistry , amide , natural product , cyclic peptide , histone deacetylase , triazole , histone deacetylase inhibitor , peptide , homogeneous , oligopeptide , combinatorial chemistry , histone , biochemistry , dna , organic chemistry , physics , thermodynamics
Fooling enzymes with mock amides : Analogues of apicidin, a cyclic‐tetrapeptide inhibitor of histone deacetylase (HDAC), were designed with a 1,4‐ or 1,5‐disubstituted 1,2,3‐triazole in place of a backbone amide bond to fix the bond in question in either a trans ‐like or a cis ‐like configuration. Thus, the binding affinity of distinct peptide conformations (see picture) could be probed. One analogue proved in some cases to be superior to apicidin as an HDAC inhibitor.