A light-activated beta-turn scaffold within a somatostatin analog: NMR structure and biological activity.
Somatostatin owes its biological activity to the presence of a well-defined beta-turn centered around the tetrapeptide Phe-Trp-Lys-Thr. We have developed a light-activated beta-turn scaffold, 1, with the ability to template a beta-turn conformation within the somatostatin tetrapeptide only upon photolysis. The three-dimensional structure of the trans cyclic peptide I obtained by NMR revealed no beta-turn conformation; however, when isomerized to the cis form II with light, the solution structure of the resulting cyclic peptide was found to contain a type II' beta-turn within the Phe-Trp-Lys-Thr sequence. Binding assays with the SRIF receptor demonstrated that the cis peptide displayed enhanced affinity for the receptor over the trans form.
Ulysse
Luckner G
LG
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA.
Chmielewski
Jean
J
D000818:Animals; D002460:Cell Line; D007536:Isomerism; D008027:Light; D051379:Mice; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D017433:Protein Structure, Secondary / Q000528:radiation effects; D017481:Receptors, Somatostatin / Q000819:agonists* / Q000378:metabolism; D013004:Somatostatin / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D009842:Oligopeptides; D017481:Receptors, Somatostatin; D013004:Somatostatin