Document Detail


Interactions of vasopressin and oxytocin receptors with vasopressin analogues substituted in position 2 with 3,3'-diphenylalanine - a molecular docking study.
MedLine Citation:
PMID:  23303737     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Vasopressin and oxytocin receptors belong to the superfamily of G protein-coupled receptors and play an important role in many physiological functions. They are also involved in a number of pathological conditions being important drug targets. In this work, four vasopressin analogues substituted at position 2 with 3,3'-diphenylalanine have been docked into partially flexible vasopressin and oxytocin receptors. The bulky residue at position 2 acts as a structural restraint much stronger in the oxytocin receptor (OTR) than in the vasopressin V2 receptor (V2R), resulting in a different location of the analogues in these receptors. This explains the different, either agonistic or antagonistic, activities of the analogues in V2R and OTR, respectively. In all complexes, the conserved polar residues serve as anchor points for the ligand both in OTR and V2R. Strong interactions of the C-terminus of analogue II ([Mpa(1) ,d-Dpa(2) ,Val(4) ,d-Arg(8) ]VP) with extracellular loop 3 may be responsible for its highest activity at V2R. It also appears that V2R adapts more readily to the docking analogues by conformational changes in the aromatic side chains triggering receptor activation. A weak activity at V1a vasopressin receptor appears to be caused by weak receptor-ligand interactions. Results of this study may facilitate a rational design of new analogues with the highest activity/selectivity at vasopressin and OTRs. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.
Authors:
Magdalena J Slusarz; Emilia Sikorska; Rafał Slusarz
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-10
Journal Detail:
Title:  Journal of peptide science : an official publication of the European Peptide Society     Volume:  -     ISSN:  1099-1387     ISO Abbreviation:  J. Pept. Sci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9506309     Medline TA:  J Pept Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.
Affiliation:
Faculty of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952, Gdańsk, Poland.
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