Glucagon-like peptide-1（GLP-1） is an endogenous insulinotropic hormone with excellent blood glucose-lowering activity, however, it is rapidly inactivated in the plasma mainly by dipeptidyl peptidase IV（DPP-IV）. To...Glucagon-like peptide-1（GLP-1） is an endogenous insulinotropic hormone with excellent blood glucose-lowering activity, however, it is rapidly inactivated in the plasma mainly by dipeptidyl peptidase IV（DPP-IV）. To overcome this problem, various N-terminal modifications of GLP-1 have been performed to prolong the in vivo biological activity, by improving the DPP-IV resistance while retaining receptor affinity and receptor activation. These studies have included modifications of His7, Ala8 or Glu9 at the N-terminus of GLP-1 and some other modifications. Among them, Ala8 substitutions with glycine（Gly8） and α-aminoisobutyric acid（Aib8） have been clinically applied in the development of diabetic therapy, such as Exenatide, Semaglutide, Albiglutide and Taspoglutide. In this review, we introduce N-terminal modifications of GLP-1 that have been reported, and discuss their potential and challenges for the treatment of type 2 diabetes.展开更多
Tumor-associated carbohydrate antigens （TACAs）, important molecular markers on tumor cells, are major targets for the development of anti-cancer vaccines. However, due to the immunotolerance and weak immunogenicity,...Tumor-associated carbohydrate antigens （TACAs）, important molecular markers on tumor cells, are major targets for the development of anti-cancer vaccines. However, due to the immunotolerance and weak immunogenicity, native TACAs cannot induce powerful immune response. The use of modified TACAs such as N-glycosides could be an alternative strategy to overcome this problem. Herein, the synthesis of N（OMe）-linked analogue of tumor-associated disaccharide antigen Thomsen-Friedenreich （TF） by the glycosylation reaction is described.展开更多
文摘Glucagon-like peptide-1（GLP-1） is an endogenous insulinotropic hormone with excellent blood glucose-lowering activity, however, it is rapidly inactivated in the plasma mainly by dipeptidyl peptidase IV（DPP-IV）. To overcome this problem, various N-terminal modifications of GLP-1 have been performed to prolong the in vivo biological activity, by improving the DPP-IV resistance while retaining receptor affinity and receptor activation. These studies have included modifications of His7, Ala8 or Glu9 at the N-terminus of GLP-1 and some other modifications. Among them, Ala8 substitutions with glycine（Gly8） and α-aminoisobutyric acid（Aib8） have been clinically applied in the development of diabetic therapy, such as Exenatide, Semaglutide, Albiglutide and Taspoglutide. In this review, we introduce N-terminal modifications of GLP-1 that have been reported, and discuss their potential and challenges for the treatment of type 2 diabetes.
基金Grant from the Ministry of Science and Technology of China(Grant No.2012ZX09502001-001)the National Natural Science Foundation of China(Grant No.81172916)
文摘Tumor-associated carbohydrate antigens （TACAs）, important molecular markers on tumor cells, are major targets for the development of anti-cancer vaccines. However, due to the immunotolerance and weak immunogenicity, native TACAs cannot induce powerful immune response. The use of modified TACAs such as N-glycosides could be an alternative strategy to overcome this problem. Herein, the synthesis of N（OMe）-linked analogue of tumor-associated disaccharide antigen Thomsen-Friedenreich （TF） by the glycosylation reaction is described.
