NOVEL ANTIHYPERTENSIVE PEPTIDE

THE PHASE I OBJECTIVE IS TO DETERMINE IF A NOVEL PEPTIDE THAT HAS BEEN SHOWN TO BIND TO AND CONVERT ARGININE VASOPRESSIN (AVP) INTO AN ANTAGONIST OF ITS POSITIVE SIGNAL FOR LYMPHOKINE PRODUCTION CAN ALSO CONVERT AVP INTO AN ANTAGONIST OF ITS VASOPRESSOR AND ANTIDIURETIC PROPERTIES. PEPTECH, INC., WILL ACHIEVE THIS OBJECTIVE BY DETERMINING IFTHE AVP-BINDING PEPTIDE CAN BLOCK: (1) THE AVP VASOPRESSOR PROPERTY OF STIMULATING PHOSPHOLIPID TURNOVER IN MURINE HEPATOCYTES, AND (2) THE AVP ANTIDIURETIC PROPERTY OF STIMULATING ACTIVATION OF ADENYLATE CYCLASE IN MURINE KIDNEYCELLS AND INCREASING THE LEVEL OF THE SECOND-MESSENGER CYCLIC AMP. IF THE AVP-BINDING PEPTIDE CAN BLOCK THE VASOPRESSOR AND ANTIDIURETIC PROPERTIES OF AVP, THEN IT WOULD BE OF CONSIDERABLE IMPORTANCE AS A DIURETIC FOR CONTROLLING HYPERTENSION AND BLOOD VESSEL CONTRACTION. THISHAS POTENTIAL FOR THE TREATMENT OF HYPERTENSION IN CARDIOVASCULAR AND METABOLIC DISORDERS. THIS APPROACH DIFFERS SIGNIFICANTLY FROM THAT OF PREVIOUS STUDIES OF AVP ANTAGONISTS IN THAT THOSE STUDIES INVOLVED COMPETITION FOR THE AVP ANTIDIURETIC AND VASOPRESSOR RECEPTORS, WHILE THIS PEPTIDE BLOCKS AVP FUNCTION BY BINDINGTO THE HORMONE ITSELF AND CONVERTING IT INTO AN ANTAGONIST OF ITS OWN ACTION.