An Influence of the Aromatic Side Chains Conformations in Positions 2 and 3 of Vasopressin Analogs on Interactions with Vasopressin and Oxytocin Receptors

Abstract

In this work, the receptor-bound conformation of nine vasopressin (CYFQNCPRG-NH 2 , AVP) analogs substituted in positions 2 or 3 with 2-aminoindane-2-carboxylic acid have been investigated using molecular modeling methods. The synthesis and functional assays of the analogs have been recently described. For comparison, the molecular dynamics of the selected analogs has been conducted. We have observed the relationship between the value of valence angle between the aromatic rings in positions 2 and 3 and the biological activity of the analogs. Both, in restricted space of the receptor cavities and unlimited continuous water environment, the same valence angles prevail, thus seem to be energetically more favorable for the particular peptides. Moreover, the residues responsible for analogs binding to the receptors have been identified.

Oxytocin and Vasopressin Agonists and Antagonists as Research Tools and Potential Therapeutics

“…Here, we focus on the properties of the most widely used peptides requested from the Manning laboratory or purchased from suppliers, together with some recently reported potential clinically useful peptides from the Ferring Laboratory ( 38 , 39 ). Space considerations preclude our being able to present or to discuss recent synthetic studies carried out in other laboratories ( 40–43 ). We also update the current status of the pre-clinical and clinical development of nonpeptide AVP and OT antagonists and of the pre-clinical development of nonpeptide OT agonists ( 44 ).…”