Conformationally homogeneous heterocyclic pseudotetrapeptides as three-dimensional scaffolds for rational drug design: receptor-selective somatostatin analogues.
A would-be amide: A 1,4-disubstituted 1,2,3-triazole was used as a surrogate for a trans amide bond to create a library of 16 diastereomeric pseudotetrapeptides as beta-turn mimetics. High-resolution structural analysis indicated that these scaffolds adopt distinct, rigid, conformationally homogeneous beta-turn-like structures (see example), some of which bind somatostatin receptor subtypes selectively, and some of which show broad-spectrum activity.
Beierle
John M
JM
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Horne
W Seth
WS
van Maarseveen
Jan H
JH
Waser
Beatrice
B
Reubi
Jean Claude
JC
Ghadiri
M Reza
MR
D018360:Crystallography, X-Ray; D015195:Drug Design; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D008968:Molecular Conformation; D009842:Oligopeptides / Q000737:chemistry*; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000737:chemistry* / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D006571:Heterocyclic Compounds; D009842:Oligopeptides; D020033:Protein Isoforms; D017481:Receptors, Somatostatin; D013004:Somatostatin