MOLECULAR MODELING-BASED STUDY OF NEW VASOPRESSIN ANALOGS AFFINITY TOWARD HUMAN NEUROHYPOPHYSEAL HORMONE RECEPTORS

摘要

The neurohypophyseal hormone arginine vasopressin (Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2; AVP) is a cyclic nonapeptide that plays several important physiological roles, such as the control of blood pressure, adrenocorticotropin hormone secretion and the regulation of water balance, mediated via three different subtypes of vasopressin receptors: V_(1a), V_(1b) and V2 (V_(1aR), V_(1bR) and V_(2R) ) and to a small extent via oxytocin (Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2; OT) receptors (OTR). In this study, nine vasopressin analogs have been investigated: analog 1: [Aic~2]AVP, analog 2: [Mpa~1,Aic~2]AVP, analog 3: [Aic~2,D-Arg~8]VP, analog 4: [Mpa~1,Aic~2,D-Arg~8]VP, analog 5: [Aic~2,Val~4]AVP, analog 6: [Mpa~1,Aic~2,Val~4]AVP, analog 7: [Aic~3]AVP, analog 8: [Mpa~1,Aic~3]AVP, analog 9: [Aic~3,D-Arg~8]VP, (Aic: 2-aminoindane-2-carboxylic acid). To determine their presumable biological activity docking and molecular modeling methods have been used. Result of this investigation will be compared with the results of functional assays (currently unavailable) and if they compatible, the molecular modeling methods could be an alternative for more expensive and time-consuming clinical tests.