Conformational studies of vasopressin analogues modified with N-methylphenylalanine enantiomers in dimethyl sulfoxide solution
✍ Scribed by Emilia Sikorska; Magdalena J. Ślusarz; Bernard Lammek
- Publisher
- Wiley (John Wiley & Sons)
- Year
- 2006
- Tongue
- English
- Weight
- 462 KB
- Volume
- 82
- Category
- Article
- ISSN
- 0006-3525
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✦ Synopsis
Abstract
The conformations of [Arg^8^]vasopressin (AVP) analogues substituted at positions 2 and 3 with N‐methylphenylalanine (MePhe) enantiomers were earlier investigated by using nuclear magnetic resonance (NMR) spectroscopy in aqueous solution. A comparison of the results obtained in H~2~O/D~2~O (9:1) and DMSO‐d~6~ has shown the structures in the first solution to be more flexible than those in DMSO‐d~6~. This is manifested by a higher percentage of minor conformations in H~2~O/D~2~O. The largest differences between the NMR spectra in both solvents were noticed for [MePhe^2^, D‐MePhe^3^]AVP (II) and [D‐Cys^1^,MePhe^2^,D‐MePhe^3^]AVP (III). Namely, in the ROESY spectra in aqueous solution, the cis/trans isomerization between MePhe^2^–DMePhe^3^ and D‐Cys^1^–MePhe^2^ for II and III, respectively, is observed, while in DMSO‐d~6~, the appropriate cross peaks indicate isomerization across the Cys^6^–Pro^7^ peptide bond. In the case of the remaining peptides, the position of cis/trans isomerization is the same in aqueous solution and in dimethyl sulfoxide. [D‐MePhe^2^,MePhe^3^]AVP (V) displays low antiuterotonic and antipressor activities, while [D‐MePhe^2,3^]AVP (IV) is a weak but selective blocker of oxytocin (OT) receptors in the uterus. The former shows similar conformational preferences as another antagonist of V~1a~ and OT receptors—namely, [Acc^2^,D‐Arg^8^]VP (Acc: 1‐aminocyclohexane‐1‐carboxylic acid)—investigated by us. In the case of IV, the cis peptide bond between residues at positions 2 and 3 might be the reason for selectivity. © 2006 Wiley Periodicals, Inc. Biopolymers 82: 603–614, 2006
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