cis-peptide bond mimetic tetrazole analogs of the insect kinins identify the active conformation.

Abstract:

:The insect kinin neuropeptides have been implicated in the regulation of water balance, digestive organ contraction, and energy mobilization in a number of insect species. A previous solution conformation study of an active, restricted-conformation cyclic analog, identified two possible turn conformations as the likely active conformation adopted by the insect kinins at the receptor site. These were a cisPro type VI beta-turn over C-terminal pentapeptide core residues 1-4 and a transPro type I-like beta-turn over core residues 2-5, present in a ratio of 60:40. Synthesis and evaluation of the diuretic activity of insect kinin analogs incorporating a tetrazole moiety, which mimics a cis peptide bond, identifies the active conformation as the former. The discovery of a receptor interaction model can lead to the development of potent agonist and antagonist analogs of the insect kinins. Indeed, in this study a tetrazole analog with D stereochemistry has been shown to demonstrate partial antagonism of the diuretic activity of natural insect kinins, providing a lead for more potent and effective antagonists of this critical neuropeptide family. The future development of mimetic agonists and antagonists of insect kinin neuropeptides will provide important tools to neuroendocrinologists studying the mechanisms by which they operate and to researchers developing new, environmentally friendly pest insect control strategies.

journal_name

Peptides

journal_title

Peptides

authors

Nachman RJ,Zabrocki J,Olczak J,Williams HJ,Moyna G,Ian Scott A,Coast GM

doi

10.1016/s0196-9781(01)00651-9

subject

Has Abstract

pub_date

2002-04-01 00:00:00

pages

709-16

issue

4

eissn

0196-9781

issn

1873-5169

pii

S0196978101006519

journal_volume

23

pub_type

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