Discovery Of Proteasome Inhibitors Targeting Multiple Myeloma And Research The Function Of Glycopeptide And Glycolipids

The research content can be divided into2sections as follows:Section OneProteasome which is a kind of protein complexes exists ubiquitously in the cells. It can degrade the protein marked by ubiquitin and adjust intracellular protein levels. So abnormality of the ubiquitin-proteasome proteolytic pathway is closely related to many diseases, especially cancer. The FDA approved two proteasome inhibitors, Bortezomib and Carfilzomib. Proteasome inhibitors have become important targets for the treatment of multiple myeloma, but its side effects and drug disease recurrence still can be settled down. This research cooperated with chemists to test the proteasome inhibition of modified Carfilzomib compounds in vitro and in vivo. Two novel proteasome inhibitors were identified which are as good as Carfilzomib. Based on our current results, the compounds have the potential to be a new drug for anti-multiple myeloma with independent intellectual property rights.In recent years, synthetic glycolipid has been widely used in many diseases such as anti-tumor, antibacterial, immune regulation research. The antitumor activity and mechanism of glycolipids is still focused by biologists and chemists. Based on these reference, work of this section is mainly around the relation between different structure of glycolipids and anti-tumor activity. It is found that the mixture of different structure glycolipids had the synergistic effect on tumor cells.Section TwoThe interaction between organism carbohydtare-protein is the biological functions of carbohydrate. This role is often consists of multivalence carbohydrate chain and specific glycoprotein receptors. Therefore, this kind of carbohydrate-protein interactions associated with the diagnosis, treatment and intervention of many diseases. It has good biological compatibility and biodegradable ability. Multivalence glycopeptides have been synthesized, and they are found that the structure with more glycopeptides can be recognized more easily. The equipped GalNAc residues endow them with the biological targeting ability and features of tumor vaccine molecules, which is benefit for biological and medical applications.