Conformational studies of vasopressin analogues modified with N‐methylphenylalanine enantiomers in dimethyl sulfoxide solution

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 This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com