Chitooligosaccharides as a novel β-secretase inhibitor

Nine kinds of hetero-chitooligosaccharides (hetero-COSs) with different degrees of deacetylation and molecular weights were prepared using an ultrafiltration (UF) membrane reactor system. In addition, their sulfated derivatives were also synthesized by a method using trimethylamine-sulfur trioxide to investigate the functional group of COSs on β-secretase inhibitory activity. 90-MMWCOSs-I, which are 90% deacetylated COSs passed through the 5 kDa membrane but not passed through the 3 kDa membrane, exhibited the highest β-secretase inhibitory activity (25–42 μM) based on molecular weight of 3 and 5 kDa. The inhibition pattern of the inhibitor was found to be a non-competitive by Dixon plot, and Ki of 90-MMWCOSs-I was 3.87–6.47 μM. Therefore, the data of this research suggest that 90-MMWCOSs-I is a good candidate target molecule to inhibit β-secretase.