Lipase-catalyzed synthesis of hydrophobically modified dextrans: Activity and regioselectivity of lipase from Candida rugosa

Vinyl decanoate-modified dextran macromolecules (DexT40-VD) were synthesized in dimethyl sulfoxide at 50°C using lipase AY from Candida rugosa for catalyzing transesterification between polysaccharide and vinyl fatty esters. The extent of dextran modification (quantified by the molar ratio of attached alkyl tails to sugar repeat units) with native-, pH-adjusted-, 18-crown-6 ether pretreated pH-adjusted-, and stepwise addition of pretreated lipase AY yielded < 3%, 49%, 64% and 96% modified dextran respectively. Lipase AY accelerated the transesterification of DexT40 from 2- to 63-fold higher than the non-catalyzed system. This procedure was extended to other acyl donors showing that modification pattern exhibited regioselectivity depending on acyl donor structure. Regioselectivity equaled between 2- and 3-OH with saturated fatty acyl donors. The 2-OH was favored for unsaturated fatty acyl donors, while sterically hindered acyl donors oriented modification toward 3-OH position. DexT40-VD at 96% modification was a water-insoluble polymer forming 150 nm diameter nanoparticles in water which can be used as drug carrier systems.