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A Light‐Activated β ‐Turn Scaffold within a Somatostatin Analog: NMR Structure and Biological Activity
Author(s) -
Ulysse Luckner G.,
Chmielewski Jean
Publication year - 2006
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2005.00337.x
Subject(s) - tetrapeptide , turn (biochemistry) , peptide , chemistry , somatostatin , stereochemistry , cyclic peptide , receptor , biological activity , biochemistry , biology , in vitro , neuroscience
Somatostatin owes its biological activity to the presence of a well‐defined β ‐turn centered around the tetrapeptide Phe‐Trp‐Lys‐Thr. We have developed a light‐activated β ‐turn scaffold, 1, with the ability to template a β ‐turn conformation within the somatostatin tetrapeptide only upon photolysis. The three‐dimensional structure of the trans cyclic peptide I obtained by NMR revealed no β ‐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′ β ‐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.