1H-nmr studies of receptor-selective substance P analogues reveal distinct predominant conformations in DMSO-d6
✍ Scribed by Dina Levian-Teitelbaum; Nancy Kolodny; Michael Chorev; Zvi Selinger; Chaim Gilon
- Publisher
- Wiley (John Wiley & Sons)
- Year
- 1989
- Tongue
- English
- Weight
- 812 KB
- Volume
- 28
- Category
- Article
- ISSN
- 0006-3525
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✦ Synopsis
Proton nrnr parameters are reported for DMSO-d, solutions of two receptor-selective substance P analogues: Ac[Arg6,Pr$lSP,,,, which is selective for the NK-1 (SP-P) receptor and [pGlu6, N-MePhe8]SP,11, which selectively activates the NK-3 (SP-N) receptor. Full peak assignments of both analogues were obtained by COSY experiments. The chemical shifts, coupling constants, and temperature coefficients of amide proton chemical shifts as well as NOESY effects and calculated side-chain rotamer populations of Phe side chains are reported for both peptides. Analysis of coupling constants and temperature coefficients together with the nuclear Overhauser enhancement spectroscopy effects suggest that Ac[Arg6, Pr$]SP,,, has a trans configuration about the Phe8-Pr$ amide bond and the preferred conformation of this analogue has a type I /?-turn. The nmr data for [pGlu6, N-MePhe8]SP,,, suggest that this peptide exists as a mixture of cis-trans isomers in which the cis isomer can preferably adopt a type VI /?-turn conformation, and the lruns isomer can adopt a y-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.