Synthesis of polymethacrylate derivatives having sulfated maltoheptaose side chains with anti-HIV activities

Anti-HIV (human immunodeficiency virus) active polymethacrylates having pen dant sulfated oligosaccharides were synthesized, and the relationship betwe en structures and biological activities of the polymethacrylates was examin ed. Acetylated 1-O-methacryloyl maltoheptaoside (MA-AcM7) was polymerized w ith AIBN as an initiator to give polymethacrylates having a pendant acetyla ted maltoheptaose in every repeating unit, poly(MA-AcM7)s. After hydroxyl g roups were recovered by deacetylation, the polymethacrylates having maltohe ptaose units, poly(MA-M7)s, were sulfated to give polymethacrylates having sulfated maltoheptaose side-chains, poly(MA-SM7)s, with degrees of sulfatio n of 1.1 to 2.7 (maximum, 3.0). These polymethacrylates including sulfated oligosaccharides exhibited low anti-HIV activities represented by the 50% p rotecting concentration (EC50) in the range of 15-62 mu g/mL and low blood anticoagulant activities around 10 unit/mg (standard dextran sulfate, 22.7 unit/mg). The anti-HIV activity increased with increasing degree of sulfati on to reach EC50 of 15-16 mu g/mL. In addition, copolymerization of MA-AcM7 with methyl methacrylate (MMA) and subsequent sulfation gave polymethacryl ates consisting of various proportions of highly sulfated maltoheptaose and MMA units. It was revealed that the anti-HIV activity increased with decre asing proportion of the sulfated oligosaccharide moiety and that a copolyme thacrylate having 22 mol % of sulfated maltoheptaose units (DS = 3.0) had a high anti-HIV activity in the EC50 of 0.3 mu g/mL. The blood anticoagulant activity increased slightly from 9 to 18 unit/mg with decreasing proportio n of the sulfated maltoheptaose units. These results suggested that the bio logical activities were influenced strongly by the spatial distance between sulfated oligosaccharide substituents in the polymethacrylate main chain. Distinction and conformation of the oligosaccharide side chains also played an important role. (C) 1999 John Wiley & Sons, Inc.