Synthesis and antidiuretic activities of novel glycoconjugates of arginine-vasopressin.
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.
Susaki
H
H
Noda Reaearch Laboratories, Drug Delivery System Institute, Ltd., Chiba, Japan.
Suzuki
K
K
Ikeda
M
M
Yamada
H
H
Watanabe
H K
HK
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
D001127:Arginine Vasopressin; D000242:Cyclic AMP