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Conformational Preferences of Proline Derivatives Incorporated into Vasopressin Analogues: NMR and Molecular Modelling Studies
Author(s) -
Sikorska Emilia,
Sobolewski Dariusz,
Kwiatkowska Anna
Publication year - 2012
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2012.01318.x
Subject(s) - chemistry , micelle , pyrrolidine , peptide , stereochemistry , side chain , proline , nuclear magnetic resonance spectroscopy , turn (biochemistry) , heteronuclear molecule , amino acid , organic chemistry , biochemistry , aqueous solution , polymer
In this study, arginine vasopressin analogues modified with proline derivatives – indoline‐2‐carboxylic acid (Ica), (2S,4R)‐4‐(naphthalene‐2‐ylmethyl)pyrrolidine‐2‐carboxylic acid (Nmp), (2S,4S)‐4‐aminopyroglutamic acid (APy) and (2R,4S)‐4‐aminopyroglutamic acid, (Apy) – were examined using NMR spectroscopy and molecular modelling methods. The results have shown that Ica is involved in the formation of the cis peptide bond. Moreover, it reduces to a great extent the conformational flexibility of the peptide. In turn, incorporation of (2S,4R)‐Nmp stabilizes the backbone conformation, which is heavily influenced by the pyrrolidine ring. However, the aromatic part of the Nmp side chain exhibits a high degree of conformational freedom. With analogues IV and V, introduction of the 4‐aminopyroglumatic acid reduces locally conformational space of the peptides, but it also results in weaker interactions with the dodecylphosphocholine/sodium dodecyl sulphate micelle. Admittedly, both analogues are adsorbed on the micelle’s surface but they do not penetrate into its core. With analogue V, the interactions between the peptide and the micelle seem to be so weak that conformational equilibrium is established between different bound states.