An investigation of position 3 in arginine vasopressin with aliphatic, aromatic, conformationally-restricted, polar and charged amino acids

✍ Scribed by S. Stoev; L.L. Cheng; A. Olma; W.A. Klis; M. Manning; W.H. Sawyer; N.C. Wo; W.Y. Chan

• Book ID: 101284115
• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 128 KB
• Volume: 5
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/(sici)1099-1387(199903)5:3<141::aid-psc180>3.0.co;2-6

✦ Synopsis

We report the solid-phase synthesis and some pharmacological properties of 23 new analogs of arginine vasopressin (AVP) which have the Phe 3 residue replaced by a broad variety of amino acids. Peptides 1 -9 have at position 3: (1) the mixed aromatic/aliphatic amino acid thienylalanine (Thi) and the aliphatic amino acids; ( 2) cyclohexylalanine (Cha); (3) norleucine (Nle); (4) Leu; (5) norvaline (Nva); (6) Val; (7) alpha-aminobutyric acid (Abu); (8) Ala; (9) Gly. Peptides 10 -23 have at position 3: the aromatic amino acids, (10) homophenylalanine (Hphe); (11) Tyr; (12) Trp; (13) 2-naphthylalanine (2-Nal); the conformationally-restricted amino acids (14) Pro; (15) 2-aminotetraline-2-carboxylic acid (Atc); the polar amino acids (16) Ser; (17) Thr; (18) Gln; and the charged amino acids (19) Asp; (20) Glu; (21) Arg; (22) Lys; ( 23) Orn. All 23 new peptides were evaluated for agonistic and, where appropriate, antagonistic activities in in vivo antidiuretic (V 2 -receptor) and vasopressor (V 1a -receptor) assays and in in vitro (no Mg 2 + ) oxytocic assays. The corresponding potencies (units/mg) in these assays for AVP are: 323 916; 36996 and 13.990.5. Peptides 1-9 exhibit the following potencies (units/mg) in these three assays: (1