Conformational preferences of proline derivatives incorporated into vasopressin analogues: NMR and molecular modelling studies
Emilia Sikorska , Dariusz Sobolewski , Anna Kwiatkowska
AbstractIn this study, arginine vasopressin analogues modi- fied with proline deri vatives – indoline-2- carboxyl ic acid (Ica) , (2S,4R)-4 -(nap hthalen e-2-yl methyl) pyrrol i- dine-2-carboxylic acid (Nmp), (2S,4S)-4-aminopyro- glutamic 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 peptid e bond . Moreove r, it reduces to a great extent the conformat ional flexibilit y of the peptid e. In turn, incorporation of (2S,4R)-Nmp stabilizes the backbone confor mat ion, whic h is heavily influe nced by the pyrrolidine ring. Howeve r, the aromatic part of the Nmp side chain exhibits a high degree of confor- mationa l freedom. With analogues IV and V , intro- ductio n of the 4-aminop yrogl umatic aci d 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 co re. With analog ue V, the int eractio ns between thepeptideandthemicelleseemtobesoweakthat conformational equilibrium is established between different bound states.
|Journal series||Chemical Biology & Drug Design, ISSN 1747-0277, (A 25 pkt)|
|Publication size in sheets||0.6|
|Keywords in English||dodecylphosphocholine/sodium dodecyl sulphate mixed micelles, molecular modelling, NMR spectroscopy, proline derivatives, vasopressin|
|Publication indicators||: 2014 = 0.9; : 2012 = 2.469 (2) - 2012=2.409 (5)|
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