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A Bioactive Somatostatin Analog without a Type II′ β‐Turn: Synthesis and Conformational Analysis in Solution
Author(s) -
Jiang Shaokai,
Gazal Sharon,
Gelerman Gary,
Ziv Ofer,
Karpov Olga,
Litman Pninit,
Bracha Moshe,
Afargan Michael,
Gilon Chaim,
Goodman Murray
Publication year - 2001
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.348
Subject(s) - chemistry , somatostatin , turn (biochemistry) , conformational isomerism , somatostatin analogue , stereochemistry , peptide , alkylation , disulfide bond , cyclic peptide , somatostatin receptor , binding affinities , affinities , receptor , combinatorial chemistry , biochemistry , molecule , organic chemistry , octreotide , biology , catalysis , neuroscience
A cyclic somatostatin analog ( 1 ) has been synthesized. Biological assays show that this compound has strong binding affinities to somatostatin hsst2 and hsst5 receptor subtypes (5.2 and 1.2 nM, respectively, and modest affinity to hsst4 (41.1 nM)). Our conformational analysis carried out in DMSO‐ d 6 indicates that this compound exists as two structures arising from the trans and cis configurations of the peptide bond between Phe 7 and N ‐alkylated Gly 8 . However, neither conformer exhibits a type II′ β‐turn. This is the first report of a potent bioactive somatostatin analog that does not exhibit a type II′ β‐turn in solution. Molecular dynamics simulations (500 ps) carried out at 300 K indicate that the backbone of compound 1 is more flexible than other cyclic somatostatin analogs formed by disulfide bonds. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd.