Chemical conjugation of interferon with pullulan and its antiviral activity

As a trial to target interferon to the liver, interferon was chemically con jugated to a water-soluble polysaccharide, pullulan, with a high inherent a ffinity for the liver Pullulan of different average molecular weights was r eacted with cyanuric chloride to prepare cyanurated pullulan derivatives,fo llowed by their coupling reaction,with interferon to obtain interferon/pull ulan conjugates. When evaluated by an in vitro antiviral assay, the biologi cal activity of interferon decreased through pullulan conjugation. The rema ining interferon activity depended on the type of pullulan to be conjugated : the lower the molecular,weight of pullulan, the higher the remaining acti vity. Conjugation with pullulan having a spacer group suppressed the activi ty loss of interferon by its chemical conjugation. It is likely that interf eron molecules are covered with pullulan to physically prevent their intera ction with the cell surface receptor resulting in a reduced antiviral activ ity of interferon. Therefore, the decreased molecular size of pullulan. and the spacer incorporation would reduce the steric hindrance of pullulan to enhance the interaction of the interferon with the receptor more frequently .