Arginine-, D-arginine-vasopressin, and their inverso analogues in micellar and liposomic models of cell membrane: CD, NMR, and molecular dynamics studies

0452828 - ÚOCHB 2016 RIV DE eng J - Journal Article
Lubecka, E. A. - Sikorska, E. - Sobolewski, D. - Prahl, A. - Slaninová, Jiřina - Ciarkowski, J.
Arginine-, D-arginine-vasopressin, and their inverso analogues in micellar and liposomic models of cell membrane: CD, NMR, and molecular dynamics studies.
European Biophysics Journal With Biophysics Letters. Roč. 44, č. 8 (2015), s. 727-743. ISSN 0175-7571. E-ISSN 1432-1017
Institutional support: RVO:61388963
Keywords : antidiuretic agonists * anionic-zwitterionic micelles * liposomes * inverso analogues
Subject RIV: CC - Organic Chemistry
Impact factor: 1.444, year: 2015
http://link.springer.com/article/10.1007/s00249-015-1071-4/fulltext.html

We describe the synthesis, pharmacological properties, and structures of antidiuretic agonists, arginine vasopressin (AVP) and [d-Arg(8)]-vasopressin (DAVP), and their inverso analogues. The structures of the peptides are studied based on micellar and liposomic models of cell membranes using CD spectroscopy. Additionally, three-dimensional structures in mixed anionic-zwitterionic micelles are obtained using NMR spectroscopy and molecular dynamics simulations. NMR data have shown that AVP and DAVP tend to adopt typical of vasopressin-like peptides beta-turns: in the 2-5 and 3-6 fragments. The inverso-analogues also adopt beta-turns in the 3-6 fragments. For this reason, their inactivity seems to be due to the difference in side chains orientations of Tyr(2), Phe(3), and Arg(8), important for interactions with the receptors. Again, the potent antidiuretic activity of DAVP can be explained by CD data suggesting differences in mutual arrangement of the aromatic side chains of Tyr(2) and Phe(3) in this peptide in liposomes rather than of native AVP. In the presence of liposomes, the smallest conformational changes of the peptides are noticed with DPPC and the largest with DPPG liposomes. This suggests that electrostatic interactions are crucial for the peptide-membrane interactions. We obtained similar, probably active, conformations of the antidiuretic agonists in the mixed DPC/SDS micelles (5:1) and in the mixed DPPC/DPPG (7:3) liposomes. Thus it can be speculated that the anionic-zwitterionic liposomes as well as the anionic-zwitterionic micelles, mimicking the eukaryotic cell membrane environment, partially restrict conformational freedom of the peptides and probably induce conformations resembling those of biologically relevant ones.
Permanent Link: http://hdl.handle.net/11104/0253733