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Keywords:

  • Bicyclic vasopressin analogues;
  • Constrained simulated annealing;
  • Molecular docking;
  • Receptor – ligand interactions

Abstract

In the Arginine Vasopressin (CYFQNCPRG–NH2, AVP) molecule, the disulfide bond between Cys1 and Cys6 forms a 20-membered ring crucial for AVP activity. The activity could be enhanced by restraining the AVP structure with additional cyclic moiety. To reduce AVP conformational flexibility, a standard link has now been added between residues at position 4, substituted with different positively charged amino acids, and Gly at position 9. The resulting AVP analogues have subsequently been docked to the vasopressin and oxytocin receptors and relaxed/geometry optimized using a Constrained Simulated Annealing (CSA) procedure. The results of our modeling suggest that the size of the additional AVP cycle is crucial for the biological activity of the analogue.