title: Synthesis and antidiuretic activities of novel glycoconjugates of arginine-vasopressin.
abstract: Arginine-vasopressin (AVP) was acylated with various acyl azides (2a-j) in pH 9.1 buffer to give AVP derivatives (11a-j) modified at the tyrosine side chain with a carbohydrate via a spacer arm. Glycoconjugates of AVP modified at the N-terminal amide (12a-e) were also synthesized from AVP and carboxylic acids (3a-e) using dicyclohexylcarbodiimide and 1-hydroxybenzotriazole as coupling agent. Analogues (11a-j) exhibited greater in vivo antidiuretic activity than AVP. AVP and glycoconjugates (12a-e) were stable in rat plasma. On the other hand, glycoconjugates (11a-i) were found to readily convert to AVP according to first order kinetics. Hence, 11a-j are considered to be prodrugs of AVP.
authors.affiliation: Noda Reaearch Laboratories, Drug Delivery System Institute, Ltd., Chiba, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Susaki
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: H
authors.initials: H
authors.lastname: Yamada
authors.forename: H K
authors.initials: HK
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004231:Diuresis / Q000187:drug effects*; D018374:LLC-PK1 Cells; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D051381:Rats; D011910:Rats, Brattleboro; D013056:Spectrophotometry, Ultraviolet; D013552:Swine; D014563:Urodynamics / Q000187:drug effects
chemical_list: D001127:Arginine Vasopressin; D000242:Cyclic AMP