In:
Annals of the New York Academy of Sciences, Wiley, Vol. 897, No. 1 ( 1999-12), p. 388-400
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 cis Pro 1‐4 β‐turn, in which the Phe1 is critical for bioactivity. Tyr‐W‐MIF‐1 prefers a trans Pro 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.
Type of Medium:
Online Resource
ISSN:
0077-8923
,
1749-6632
DOI:
10.1111/nyas.1999.897.issue-1
DOI:
10.1111/j.1749-6632.1999.tb07908.x
Language:
English
Publisher:
Wiley
Publication Date:
1999
detail.hit.zdb_id:
2834079-6
detail.hit.zdb_id:
211003-9
detail.hit.zdb_id:
2071584-5
SSG:
11
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