ΣΥΝΘΕΣΗ ΚΑΙ ΦΑΡΜΑΚΟΛΟΓΙΚΗ ΔΡΑΣΗ ΑΝΑΛΟΓΩΝ ΤΗΣ ΑΓΓΕΙΟΤΕΝΣΙΝΗΣ ΙΙ ΜΕ ΠΕΡΙΟΡΙΣΜΕΝΗ ΔΙΑΜΟΡΦΩΤΙΚΗ ΕΛΕΥΘΕΡΙΑ

Abstract

THE SYNTHESIS AND THE PHARMACOLOGICAL PROPERTIES OF TWENTY-ONE NEW ANGIOTENSIN II (AII) ANALOGUES. THIS STUDY WAS PERFORMED FOR FURTHER UNDERSTANDING OF THE STRUCTURE-ACTIVITY RELATIONSHIPS, AND THE IMPROVEMENT OF NEW POTENT LONG-ACTING AII ANTAGONISTS WITH THERAPEUTIC USE. THE PEPTIDES WERE SYNTHESIZED BY MERRIFIELD'S SOLID PHASE PROCEDURE, PURIFIED BY REVERSED- PHASE HPLC. THECOMPOUNDS WERE TESTED ON FABBIT AORTA STRIPS, IN THE RAT ISOLATA UTERUS ANDBORINE ADVENOCORTICAL MEMBRANES. THE CONCLUSION OF THEIR STUDIES CONCERNING STRUCTURE ACTIVITY RELATIONSHIPS INDICATE THAT : -THE PRESENCE OF Β-COOH AT THE TERMINAL PART OF AII IS CRITICAL FOR BOTH BINDING AFFINITY AND STIMULATION /-AN INCREASED IN BASICITY AT THE N-TEREMINAL NITROGEN ATOM OF AII IS NOT THE ONLY REASON FOR INCREASED POTENCY./-THE PRESENCE OF AIB0 IN THE N-TERMINAL RESTRICTS THE ROLE CONFORMATION OF THE PEPTIDE./-THE OH- OF TYR4 IS IMPORTANT FOR THE AGONIST ACTIVITY OF AII./-THE SIZE AND THE SPABE OF THE N-TERMINAL RESIDUE OF SARMESIN APPEARS TO BE SUBJECT TO UNSUALLY SEVERE RESTRICTIONS./-THE PROSENCE OF AIB7 PROVIDES STERIC HYNDRANCE./-THE POSITIVE CHARGE LOCATED ON THE GUANIDINE GROUP OF ARG2 RESIDUE IS MANDATORY FOR THE BIOLOGICAL ACTIVITY.(ABSTRACT TRUNCATED)