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- Title
Comparison of Active Conformations of the Insectatachykinin/tachykinin and Insect Kinin/Tyr-W-MIF-1 Neuropeptide Family Pairs.
- Authors
NACHMAN, RONALD J.; MOYNA, GUILLERMO; WILLIAMS, HOWARD J.; ZABROCKI, JANUSZ; ZADINA, JAMES E.; COAST, GEOFFREY M.; BROECK, JOZEF
- Abstract
A bstract: A comparison of solution conformations of active, restricted-conformation analogues of two sequence-similar insect/vertebrate neuropeptide family pairs shed light on the potential existence of molecular evolutionary relationships. Analogues of the locustatachykinins and the mammalian tachykinin substance P, containing a sterically hindered Aib-NMePhe/Tyr residue block, share similar low-energy turn conformations incorporating a cis peptide bond. Conversely, restricted conformation analogues of the insect kinins and the mammalian opiate peptide Tyr-W-MIF-1, with near identical C-terminal tetrapeptide sequences, adopt different conformations. The insect kinins adopt a cisPro 1-4 β-turn, in which the Phe1 is critical for bioactivity. Tyr-W-MIF-1 prefers a transPro 2-5 turn, and an additional N-terminal Phe severely inhibits μ-opiate receptor binding. Comparisons of the chemical/conformational requirements for receptor interaction are consistent with a distant evolutionary relationship between the insectatachykinins and tachykinins, but not between the insect kinins and Tyr-W-MIF-1. Therefore, analogues of the insect kinins with pest control potential can be readily designed to avoid mammalian interactions.
- Publication
Annals of the New York Academy of Sciences, 1999, Vol 897, Issue 1, p388
- ISSN
0077-8923
- Publication type
Article
- DOI
10.1111/j.1749-6632.1999.tb07908.x