ISSN:
0006-3525
Keywords:
Chemistry
;
Polymer and Materials Science
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
In its dimeric form neuropeptide Y (NPY) folds into a compact structure in which the antiparallel oriented proline and α-helices apparently associate to form a primitive hydrophobic core. To investigate the contribution of helical stability to the receptor binding activity of NPY and its N-terminal deletion fragments, we synthesized and studied the solution conformational properties and in vitro activities of NPY, Nα-acetyl-NPY2-36, NPY15-36, Nα-propinonly-NPY15-36, and Nα-succinyl-NPY15-36 is significantly less helical than both NPY and Nα-acetyl-NPY2-36, and this decreased helical potential is attributed of the absence of the intramolecular stabilizing interaction afforded by the proline helix in the latter analogues. However, in accord with the helix dipole model, the helical potential of NPY15-36 is significantly increased by N-terminal succinlyation, whereas propionylation has no effect. In addition to an increase in helical potential, Nα-succinyl-NPY15-36 is 2.5 and 4.6 times more active than NPY15-36 and Nα-propionly-NPY15-36, respectively and is equipotent with Nα-acteyl-NPY2-36 in displacing 1mM[3H]-NPY from specific binding sites in rat brain membranes. The demonstration of positive correlation between % α-helix content and in vitro binding activity suggests that the helical potential of N-terminal NPY deletion fragments contributes to their in vitro activity in the rat brain, and that a second role of the proline helix might be to stabilize the receptor-active conformation of the NPY α-helix. © 1993 John Wiley & Sons, Inc.
Additional Material:
7 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/bip.360330806
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