1d1e

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SOLUTION STRUCTURE OF LACTAM-BRIDGED C-TERMINAL ANALOGUE-II OF NEUROPEPTIDE Y

Overview

The importance of helical structure in an analogue of NPY selective for, the Y2 receptor, Ac[Leu28,31]NPY24-36, has been investigated by, introducing a lactam bridge between positions 28 and 32. The resulting, analogue, Ac-cyclo28/32[Ala24,Lys28,Leu31,Glu32]NPY24-36, is a potent, Y2-selective agonist. Structural analysis by NMR shows that this analogue, forms a helical structure in a 40% trifluoroethanol/water mixture, whereas, in water only the region around the lactam bridge (Lys28-Glu32) adopts, helical-like structure, with both N- and C-termini being poorly defined., The observation of well-defined helical structure in aqueous TFE contrasts, with that reported for a similar analogue, Ac-cyclo28/32[Lys28,Glu32]NPY25-36 (Rist et al. FEBS Lett. 1996, 394, 169-173), which consisted of a hairpin-like structure that brought the N-, and C-termini into proximity. We have therefore determined the structures, of this analogue, as well as those of, Ac-cyclo28/32[Ala24,Lys28,Leu31,Glu32]NPY24-36 and, Ac-cyclo28/32[Ala24,Lys28,Glu32]NPY24-36, under identical solution, conditions (30% TFE/H2O mixture at 308 K) and find essentially the same, helical structure in all three peptides. These findings support the, proposal that these Y2-selective analogues adopt a helical structure when, bound to the Y2 receptor.

About this Structure

1D1E is a Protein complex structure of sequences from [1] with ACE and NH2 as ligands. Full crystallographic information is available from OCA.

Reference

Stabilization of the helical structure of Y2-selective analogues of neuropeptide Y by lactam bridges., Yao S, Smith-White MA, Potter EK, Norton RS, J Med Chem. 2002 May 23;45(11):2310-8. PMID:12014969

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