1D1E

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

Summary for 1D1E

• Entry DOI: 10.2210/pdb1d1e/pdb
• Related: 1D0W
• NMR Information: BMRB: 5215
• Descriptor: C-TERMINAL ANALOGUE OF NEUROPEPTIDE Y, A POTENT Y2 RECEPTOR AGONIST (1 entity in total)
• Functional Keywords: lactam-bridge, helix, neuropeptide
• Total number of polymer chains: 1
• Total formula weight: 1704.98

Authors

Yao, S.,Norton, R.S. (deposition date: 1999-09-15, release date: 2000-06-17, Last modification date: 2024-10-16)

Primary citation

Yao, S.,Smith-White, M.A.,Potter, E.K.,Norton, R.S.
Stabilization of the helical structure of Y2-selective analogues of neuropeptide Y by lactam bridges.
J.Med.Chem., 45:2310-2318, 2002

PubMed Abstract: 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.

PubMed: 12014969
DOI: 10.1021/jm010543z

Experimental method

SOLUTION NMR