Review: Advances in preparation of chitooligosaccharides with heterogeneous sequences and their bioactivity

Chitooligosaccharides has attracted increasing attention due to their diverse bioactivities and potential application. Previous studies on the bioactivity of chitooligosaccharides were mostly carried out using a mixture. The structure-function relationship of chitooligosaccharides is not clear. Recently, it is confirmed that chitooligosaccharides with different degrees of polymerization play different roles in many bioactivities. However, heterogeneous chitooligosaccharides with a single degree of polymerization is still a mixture of many uncertain sequences and it is difficult to determine which structure is responsible for biological effects. Therefore, an interesting and challenging field of studying chitooligosaccharides with heterogeneous sequences has emerged. Herein, we reviewed the current methods for preparing heterogeneous chitooligosaccharides, including chemical synthesis, separation techniques and enzymatic methods. Advances in the bioactivities of chitooligosaccharides with heterogeneous sequences are also reviewed.