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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010NMR Studies of Vasopressin Analogues Modified withIndoline-2-carboxylic Acid in Position 2 inDodecylphosphocholine MicelleEmilia Lubecka, Emilia Sikorska, Anna Kwiatkowska,and Jerzy CiarkowskiFaculty of Chemistry, University of Gdańsk, 80-952, Gdańsk, PolandIntroductionWe used NMR spectroscopy and molecular modeling methods to find dominantconformations of two vasopressin analogues: [Mpa 1 ,L-Ica 2 ]AVP (I) and [Mpa 1 ,L-Ica 2 ,D-Arg 8 ]VP (II) (Mpa=3-mercaptopropionic acid; Ica=indoline-2-carboxylic acid). The NMRspectra were recorded in the mixture of phosphate buffer, pH=7.4 and DMSO-d 6 (1:1) inthe presence of dodecylphosphocholine (DPC) micelle. The current model for peptidehormone interactions with their receptors suggests that the bioactive conformation of thepeptide is induced upon association with the cell membrane followed by a two-dimensionaldiffusion process, whereby the peptide is recognized and then interacts with the receptor[1]. Therefore, exploring the conformational and dynamic properties of a ligand in amembrane-mimicking environment can contribute to better understanding of the molecularfeatures involved in their interactions with the target receptor. Dodecylphosphocholine(DPC) micelle is considered to be a good model of eukaryotic cell membrane [1].Pharmocological studies have shown that II is a moderate oxytocin antagonists,whereas I is a very weak agonist. Both compounds exhibit only negligible antidiureticactivity and are devoid of the pressor potency. Analogue II reveals also significantly higheraffinity to the OT receptors than I (unpublished).Table 1. Structural statistics for the set of the last 100 conformations of [Mpa 1 ,L-Ica 2 ]AVP(I) and [Mpa 1 ,L-Ica 2 ,D-Arg 8 ]VP (II)PeptideStatistic[Mpa 1 ,L-Ica 2 ]AVP (I)[Mpa 1 ,L-Ica 2 ,D-Arg 8 ]VP (II)The clusters I II I II III IVThe numbers ofconformationsAtomic r.m.s.differences (Å):Backbone atoms1-6Heavy atoms 1-6Conformationalproperties:DominantreversestructuresMost popularhydrogen bonds20 80 23 50 9 180.2631.0982,3β I/IV3,4βI',III'/IV0.4221.1902,3β I/IV4,5β I,I'/II'0.4731.1180.6291.5247,8β II 2,3β a,b3,4βI,IV/VII4,5β IV b5,6β IV b7,8β II/IV0.4601.1362,3β a4,5β a7,8β II0.3430.9042,3β I'3,4β IV/VII7,8β II/IVHN 3 -CO 1HN 5 -CO 1 HN 3 -CO 1HN 4 -CO 1 HN 9 -CO 6 HN 4 -CO 1HN 6 -CO 4HN 9 -CO 6a different types of β-turns; b occurs in approximately 50% of the conformation428