Coupling of antiviral nucleoside analogs to lactosaminated human albumin by using the imidazolides of their phosphoric esters.
Liver targeting of antiviral nucleoside analogs can be obtained by conjugating these drugs with the hepatotropic molecule lactosaminated serum albumin. We describe a new coupling procedure which uses the imidazolides of the phosphoric ester derivatives of the drugs in an alkaline medium. By this procedure conjugates are obtained with a high drug/carrier molar ratio and without the unwanted protein chemical changes produced by carbodiimides usually employed for this coupling.
Fiume
L
L
Department of Experimental Pathology, University of Bologna, Italy.
Busi
C
C
Di Stefano
G
G
Mattioli
A
A
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D004952:Esters / Q000138:chemical synthesis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D007526:Isoelectric Point; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D009705:Nucleosides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D010756:Phosphoric Acids / Q000138:chemical synthesis; D010758:Phosphorus; D051381:Rats; D012709:Serum Albumin / Q000138:chemical synthesis* / Q000494:pharmacology; D001084:Vidarabine Phosphate / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology
D000998:Antiviral Agents; D004337:Drug Carriers; D004952:Esters; D007093:Imidazoles; D009705:Nucleosides; D010756:Phosphoric Acids; D012709:Serum Albumin; C046912:lactosaminated serum albumin; D001084:Vidarabine Phosphate; D010758:Phosphorus