title: Probing the bioactive conformation of an archetypal natural product HDAC inhibitor with conformationally homogeneous triazole-modified cyclic tetrapeptides.
abstract: 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.
authors.affiliation: Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: W Seth
authors.initials: WS
authors.lastname: Horne
authors.forename: Christian A
authors.initials: CA
authors.lastname: Olsen
authors.forename: John M
authors.initials: JM
authors.lastname: Beierle
authors.forename: Ana
authors.initials: A
authors.lastname: Montero
authors.forename: M Reza
authors.initials: MR
authors.lastname: Ghadiri
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D010456:Peptides, Cyclic / Q000737:chemistry*; D011487:Protein Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D010456:Peptides, Cyclic; D014230:Triazoles; C102351:apicidin; D006655:Histone Deacetylases