Structural requirements for alkylglycoside-type renal targeting vector

Purpose. We have previously shown Glc-S-C7-Me (octyl beta-D-thioglucoside) exhibits renal targeting potential in vivo in addition to its specific bind ing to the renal membrane fraction in vitro. Thus, "alkylglycoside" is cons idered to be a novel targeting vector for the kidney (1,2). The present stu dy is designed to clarify the structural requirements for alkylglycoside as a renal targeting vector. Methods. Inhibitory effects of various sugars and glycosides on H-3-Glc-S-C 7-Me binding to the kidney membrane fraction were evaluated by a centrifuga tion 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 gre ater 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 essen tial; OH at 2 position can have either orientation or be deleted. As far as the alkyl moiety is concerned, the length, branching and electrical enviro nment in the region of the glycoside bond are important; aromatic structure s can substitute for the alkyl portion; the preferred glycoside bonding ato m is as follows: S > NH > O. Conclusions. The structural requirements for the renal targeting vector hav e been identified to be as follows: a hydrophobic group (alkyl chain or aro matic ring) should be introduced to a sugar (D-glucose, D-mannose, or 2-deo xy-D-glucose) via a beta-glycoside binding atom (S > NH > O).