Structural requirements for alkylglycoside-type renal targeting vector.
OBJECTIVE
We have previously shown Glc-S-C7-Me (octyl beta-D-thioglucoside) exhibits renal targeting potential in vivo in addition to its specific binding to the renal membrane fraction in vitro. Thus, "alkylglycoside" is considered to be a novel targeting vector for the kidney (1,2). The present study is designed to clarify the structural requirements for alkylglycoside as a renal targeting vector.


METHODS
Inhibitory effects of various sugars and glycosides on 3H-Glc-S-C7-Me binding to the kidney membrane fraction were evaluated by a centrifugation method.


RESULTS
As far as the sugar moiety is concerned, no other sugars except D-aldohexose and D-aldohexose derivatives (containing F, S, and N) showed greater inhibition than D-glucose. Therefore, octylthio derivatives of various D-aldohexose were prepared and their inhibitory effects were investigated. The following findings were obtained: Equatorial OH at 4 position is essential; OH at 2 position can have either orientation or be deleted. As far as the alkyl moiety is concerned, the length, branching and electrical environment in the region of the glycoside bond are important; aromatic structures can substitute for the alkyl portion; the preferred glycoside bonding atom is as follows: S > NH > O.


CONCLUSIONS
The structural requirements for the renal targeting vector have been identified to be as follows: a hydrophobic group (alkyl chain or aromatic ring) should be introduced to a sugar (D-glucose, D-mannose, or 2-deoxy-D-glucose) via a beta-glycoside binding atom (S > NH > O).
Suzuki
K
K
Pharmaceutical Research Center, Meiji Seika Kaisha, LTD., Yokohama-shi, Kanagawa, Japan. kokichi_suzuki@meiji.co.jp
Ando
T
T
Susaki
H
H
Mimori
K
K
Nakabayashi
S
S
Sugiyama
Y
Y
D000818:Animals; D002241:Carbohydrates / Q000494:pharmacology; D003902:Detergents / Q000378:metabolism / Q000493:pharmacokinetics; D006027:Glycosides / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism*; D008566:Membranes / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D013329:Structure-Activity Relationship; D013863:Thioglucosides / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000493:pharmacokinetics
D002241:Carbohydrates; D003902:Detergents; D006027:Glycosides; D013863:Thioglucosides; C042989:n-octyl-beta-D-thioglucopyranoside