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1 H‐nmr studies of receptor‐selective substance P analogues reveal distinct predominant conformations in DMSO‐d 6
Author(s) -
LevianTeitelbaum Dina,
Kolodny Nancy,
Chorev Michael,
Selinger Zvi,
Gilon Chaim
Publication year - 1989
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360280108
Subject(s) - chemistry , chemical shift , conformational isomerism , amide , stereochemistry , hydrogen bond , nuclear magnetic resonance spectroscopy , proton , side chain , nuclear overhauser effect , proton nmr , coupling constant , two dimensional nuclear magnetic resonance spectroscopy , turn (biochemistry) , carboxamide , peptide bond , cis–trans isomerism , peptide , molecule , organic chemistry , physics , quantum mechanics , polymer , particle physics , biochemistry
Proton nmr parameters are reported for DMSO‐d 6 solutions of two receptor‐selective substance P analogues: Ac[Arg 6 , Pro 9 ]SP 6‐11 , which is selective for the NK‐1 (SP‐P) receptor and [pGlu 6 , N‐MePhe 8 ]SP 6‐11 , which selectively activates the NK‐3 (SP‐N) receptor. Full peak assignments of both analogues were obtained by COSY experiments. The chemical shifts, coupling constants, and temperature coefficients of amide proton chemical shifts as well as NOESY effects and calculated side‐chain rotamer populations of Phe side chains are reported for both peptides. Analysis of coupling constants and temperature coefficients together with the nuclear Overhauser enhancement spectroscopy effects suggest that Ac[Arg 6 , Pro 9 ]SP 6‐11 has a trans configuration about the Phe 8 ‐Pro 9 amide bond and the preferred conformation of this analogue has a type I β‐turn. The nmr data for [pGlu 6 , N‐MePhe 8 ]SP 6‐11 suggest that this peptide exists as a mixture of cis – trans isomers in which the cis isomer can preferably adopt a type VI β‐turn conformation, and the trans isomer can adopt a γ‐turn conformation. There are indications that the two last turns are stabilized by a hydrogen bond between the syn carboxamide proton and the pGlu ring carbonyl.