Renal targeting of arginine-vasopressin by modification with carbohydrates at the tyrosine side chain.
To extend the utility of a renal targeting system using carbohydrate derivatives, we investigated the in vivo tissue distribution in rats of arginine-vasopressin (AVP) derivatives modified at the phenolic hydroxy group of tyrosine by linking it to some sugars, namely D-glucose, D-galactose, D-mannose and L-fucose, via an octamethylene group. The glycosyl and mannosyl derivatives of AVP exhibit renal-selective distribution in vivo. In addition, the glucosyl and mannosyl derivatives exhibited specific binding to the kidney microsomal fraction in vitro. Modification with D-glucose or D-mannose at the tyrosine side chain is a suitable methodology for renal targeting, as well as at N-terminal amine.
Susaki
H
H
Noda Research Laboratories, Drug Delivery System Institute, Ltd., Chiba, Japan.
Suzuki
K
K
Yamada
H
H
Okuno
S
S
Watanabe
H K
HK
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D016503:Drug Delivery Systems; D005947:Glucose / Q000378:metabolism*; D006031:Glycosylation; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008358:Mannose / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014443:Tyrosine / Q000378:metabolism*
D001127:Arginine Vasopressin; D014443:Tyrosine; D005947:Glucose; D008358:Mannose