Micelle-bound conformations of neurohypophyseal hormone analogues modified with a Cα-disubstituted residue: NMR and molecular modelling studies

Abstract

In this study, by applying a combined approach of NMR measurements and molecular modelling, the conformations and the interactions with membrane-like environment of five arginine vasopressin (AVP) or oxytocin (OT) analogues modified with Cα-disubstituted cis-1-amino-4-phenylcyclohexane-1-carboxylic acid in position 2 have been determined. In addition, the AVP analogues were prepared in N-acylated forms with various bulky acyl groups. All of the peptides studied interacted with the mixed dodecylphosphocholine:sodium dodecyl sulphate micelle, providing a model of biological membrane. A different polarities of the AVP- and OT-like peptides resulted in their different position relative to the micelle surface. Thus, the arrangement of the former was nearly perpendicular, whereas the latter was rather parallel to the micelle's surface. Moreover, the results of our studies have shown that the binding sites for antagonists may be overlapped with that for agonists, as well as it may be quite different. Nevertheless, the aromatic–aromatic contacts represent the most important interactions for antagonists, whereas the hydrophilic interactions seem to be crucial for agonists.

Keywords:

• Cα-disubstituted amino acid
• micelle-bound structure
• NMR studies
• oxytocin
• vasopressin

Acknowledgements

This work was supported by the Polish Scientific Research Committee Grant No. N204 181736. Partial funding was also provided by the University of Gdańsk, DS 8453-4-0169-11. The calculations were carried out in the Academic Computer Centre (TASK) in Gdańsk, Poland.