Preparation of O-acylated low-molecular-weight carrageenans with potent anti-HIV activity and low anticoagulant effect

Depolymerization of λ- and κ-carrageenan was performed using ultrasonication at room temperature in the presence of ferrous ions, ascorbic acid and ethylenediaminetetraacetic acid. Tetrabutylammonium (TBA) salts of each depolymerized carrageenan were dissolved in N, N-dimethylformamide (DMF) and acylated by carboxylic acid anhydride at room temperature in the presence of dimethylaminopyridine and tributylamine as catalysts. The TBA salts of acylated carrageenans were dissolved in DMF and sulfated by pyridine–sulfur trioxide. The anti-HIV activities of each preparation were determined in a system in which MT-4 cells were infected with HTLV-III B. Sulfated samples prepared from low butanoylated or low hexanoylated derivatives had higher anti-HIV activities than dextran sulfate used as reference. Anticoagulant activity of these preparations was determined from the measurement of activated partial thromboplastin time (APTT). The butanoylated derivatives of λ-carrageenan with a degree of substitution of 1.1–1.5 had anticoagulant activities of 6.7–8.5 unit/mg, which were distinctly lower than that of dextran sulfate (avg. mol. wt. 0.7×10 4), 23.4 unit/mg. This result indicated clearly the decreasing effect of the substituted acyl group on anticoagulant activity. Hemolytic activity of these preparations was negligible.