title: Conjugation of adenine arabinoside 5'-monophosphate to arabinogalactan: synthesis, characterization, and antiviral activity.
abstract: A conjugate consisting of the antiviral nucleotide analogue adenine arabinoside 5'-monophosphate (araAMP, vidarabine monophosphate) and the naturally occurring polysaccharide arabinogalactan was synthesized. The conjugate consisted of 7.9 araAMP residues per molecule of arabinogalactan. The proposed structure of the conjugate was consistent with 13C NMR spectroscopic studies. Daily injections of the conjugate, at a dose of 3 mg of araAMP/kg, into woodchuck carriers of woodchuck hepatitis virus (WHV) decreased serum levels of WHV DNA. A dose of 3 mg/kg of unconjugated araAMP was ineffective, while a higher dose of araAMP (15 mg/kg, 14 days) produced a drop in WHV DNA. After cessation of dosing with the conjugate, serum viral DNA levels remained depressed for 42 days. In contrast, after cessation of dosing with araAMP, WHV DNA rapidly returned to original levels.
authors.affiliation: Advanced Magnetics Inc., Cambridge, Massachusetts 02138-1038, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Enriquez
authors.forename: C
authors.initials: C
authors.lastname: Jung
authors.forename: L
authors.initials: L
authors.lastname: Josephson
authors.forename: B C
authors.initials: BC
authors.lastname: Tennant
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D037263:Asialoglycoprotein Receptor; D002353:Carrier State; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004279:DNA, Viral / Q000737:chemistry; D005260:Female; D005685:Galactans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006509:Hepatitis B / Q000188:drug therapy*; D017919:Hepatitis B Virus, Woodchuck; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008392:Marmota / Q000821:virology*; D051379:Mice; D008970:Molecular Weight; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D001084:Vidarabine Phosphate / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D037263:Asialoglycoprotein Receptor; D004279:DNA, Viral; D005685:Galactans; D011956:Receptors, Cell Surface; D001084:Vidarabine Phosphate; C005653:arabinogalactan