Synthesis of sulfonated amino-polysaccharides having anti-HIV and blood anticoagulant activities.
Sulfonated 3-amino-3-deoxy-(1-->6)-alpha-D-allopyranans were synthesized to elucidate the relationship between structure and such specific biological activities as anti-HIV and blood anticoagulant activities. Ring-opening copolymerization of 1,6-anhydro-3-azido-2,4-di-O-benzyl-3-deoxy-beta-D-allopyranose 1 with 1,6-anhydro- 2,3,4-tri-O-benzyl-beta-D-allopyranose 2 with PF5 catalyst gave copolymers having various proportions of the 1 unit. 13C NMR spectroscopy showed the resulting copolymers to have alpha-(1-->6)-stereoregularity, and the monomer reactivity ratios were calculated to be r1 = 0.92 and r2 = 1.11 by the Kelen-Tüdös method. Reduction of the azido groups and subsequent debenzylation of the copolymers afforded new amino-polysaccharides consisting of 3-amino-3-deoxy-allose and allose units. Sulfonation of 3-amino-3-deoxy-(1-->6)-alpha-D-allopyranan and copolysaccharides consisting of 3-amino-allose and allose or glucose units was performed with piperidine-N-sulfonic acid to give polysaccharides containing sulfoamido and sulfonate groups in good yields. The sulfoamido-copolysaccharides containing of 3-amino-3-deoxy-allose and glucose units exhibited high anti-HIV activities manifested by the 50% protecting concentration (EC50) of 0.2-0.5 mg/mL and low cytotoxicity shown by a 50% cytotoxic concentration (CC50) of > 1000 micrograms/mL. The sulfoamido-copolysaccharides containing 3-amino-allose and allose units had somewhat lower anti-HIV activities (EC50 = 0.8-0.9 microgram/mL) and slightly higher cytotoxicities (CC50 = 740-797 micrograms/mL). In addition, it was found that the blood anti-coagulant activity increased, with increasing proportion of the amino-allose unit, from 30 to 58 unit/mg (standard dextran sulfate, 22.7 unit/mg). These results suggest that the sulfonated 3-amino-3-deoxyallose unit plays important roles on both anti-HIV and blood anticoagulant activities.
Hattori
K
K
Polymer Science Department, Graduate School of Science, Hokkaido University, Sapporo, Japan.
Yoshida
T
T
Nakashima
H
H
Premanathan
M
M
Aragaki
R
R
Mimura
T
T
Kaneko
Y
Y
Yamamoto
N
N
Uryu
T
T
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis*; D000925:Anticoagulants / Q000138:chemical synthesis*; D002417:Cattle; D002460:Cell Line; D005947:Glucose; D009682:Magnetic Resonance Spectroscopy; D011134:Polysaccharides / Q000138:chemical synthesis*; D013431:Sulfates
D019380:Anti-HIV Agents; D000925:Anticoagulants; D011134:Polysaccharides; D013431:Sulfates; D005947:Glucose