Conformational preferences of proline derivatives incorporated into vasopressin analogues: NMR and molecular modelling studies

Emilia Sikorska , Dariusz Sobolewski , Anna Kwiatkowska

Abstract

In 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.
Author Emilia Sikorska (FCh / DOCh / PBSB)
Emilia Sikorska,,
- Pracownia Badań Strukturalnych Biopolimerów
, Dariusz Sobolewski (FCh / DOCh / LChB)
Dariusz Sobolewski,,
- Laboratory of Chemistry of Biopolymers
, Anna Kwiatkowska (FCh / DOCh)
Anna Kwiatkowska,,
- Department of Organic Chemistry
Journal seriesChemical Biology & Drug Design, ISSN 1747-0277, (A 25 pkt)
Issue year2012
Vol79
No4
Pages535-547
Publication size in sheets0.6
Keywords in Englishdodecylphosphocholine/sodium dodecyl sulphate mixed micelles, molecular modelling, NMR spectroscopy, proline derivatives, vasopressin
ASJC Classification1313 Molecular Medicine; 1303 Biochemistry
DOIDOI:10.1111/j.1747-0285.2012.01318.x
URL https://doi.org/10.1111/j.1747-0285.2012.01318.x
Languageen angielski
Score (nominal)25
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2014 = 0.9; WoS Impact Factor: 2012 = 2.469 (2) - 2012=2.409 (5)
Citation count*
Cite
Share Share

Get link to the record


* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
Back