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.
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA.
Luckner G
LG
Ulysse
Jean
J
Chmielewski
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