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Comparison of insect kinin analogs with cis ‐peptide bond motif 4‐aminopyroglutamate identifies optimal stereochemistry for diuretic activity
Author(s) -
Kaczmarek Krzysztof,
Williams Howard J.,
Coast Geoffrey M.,
Scott A. Ian,
Zabrocki Janusz,
Nachman Ronald J.
Publication year - 2006
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.20613
Subject(s) - chemistry , peptidomimetic , kinin , insect , peptide , stereochemistry , diuretic , peptide bond , cyclic peptide , biochemistry , receptor , pharmacology , bradykinin , botany , biology
Abstract The insect kinins are present in a wide variety of insects and function as potent diuretic peptides, though they are subject to rapid degradation by internal peptidases. Insect kinin analogs incorporating stereochemical variants of ( 2S,4S )‐4‐aminopyroglutamate (APy), a cis ‐peptide bond motif, demonstrate significant activity in a cricket diuretic assay. Insect kinin analogs containing ( 2R,4R )‐APy, ( 2S,4R )‐APy and ( 2S,4S )‐APy are essentially equipotent on an insect diuretic assay, with EC 50 values of about 10 −7 M , whereas the ( 2R,4S )‐APy analog is at least 10‐fold more potent (EC 50 = 7 × 10 −9 M ). Conformational studies in aqueous solution indicate that the ( 2R,4S )‐APy analog is considerably more flexible than the other three variants, which may explain its greater potency. The work identifies the optimal stereochemistry for the APy scaffold with which to design biostable, peptidomimetic analogs with the potential to disrupt critical insect kinin‐regulated processes in insects. © 2006 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88:1–7, 2007. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com.