A series of carbamate-containing sialyltransferase inhibitors were designed and synthesized to simulate phosphate-linked CMP-Neu5Ac.Their inhibitory activities were assayed against recombinant human ST3Gal I and ST6Ga...A series of carbamate-containing sialyltransferase inhibitors were designed and synthesized to simulate phosphate-linked CMP-Neu5Ac.Their inhibitory activities were assayed against recombinant human ST3Gal I and ST6Gal I by using the Schmidt’s HPLC-based assay.The synthetic compound 15 g showed moderate inhibitory activity.These findings implied that carbamate might serve as a bioisosteric replacement for a phosphate group in sialyltransferase inhibitor design to improve the membrane permeability.展开更多
BACKGROUND: The incidence of extrahepatic bile duct carcinoma (EBDC) has been increasing, especially in aged people, but the glycobiology of the tumor is not elucida- ted. In this study we investigated the expressions...BACKGROUND: The incidence of extrahepatic bile duct carcinoma (EBDC) has been increasing, especially in aged people, but the glycobiology of the tumor is not elucida- ted. In this study we investigated the expressions of three glycosyltransferases in 35 patients with EBDC and 35 pa- tients with benign biliary duct disease (BBDD) as well as their clinicopathological significance. METHOD: The patients were divided into several sub- groups by tumor differentiation, TNM stage, and invasion by the standards recommended by UICC. Tumor samples were immediately frozen in liquid nitrogen after resection, followed by mRNA determination of enzymes in the tissue using a mRNA selective reverse trancriptase-polymerase chain reaction kit. The mRNA levels of different groups were semi-quantitatively compared. RESULTS: The mRNA levels of N-acetylglucosaminyltrans- ferase V (GnT-V) and a subtype of α2,3 sialyltransferases for N-glycans, ST3Gal- were elevated 7.75 and 5.39 times in EBDC as compared with BBDD, respectively, and they were correlated to several clinicopathological factors including tumor advancement, differentiation, metastasis, and invasiveness. The mRNA expression of another sialyl- transferase, ST6Gal- , was also 0.63-fold higher in EBDC than in BBDD, but not involved in the clinicopathological characteristics. CONCLUSION: The elevated expression of these three gly- cosyltransferases can be considered as an important molecu- lar event in the occurrence and progression of EBDC.展开更多
Sialic acids are common terminal carbohydrates on cell surface.Together with internal carbohydrate structures,they play important roles in many physiological and pathological processes.In order to obtain α2–3-sialyl...Sialic acids are common terminal carbohydrates on cell surface.Together with internal carbohydrate structures,they play important roles in many physiological and pathological processes.In order to obtain α2–3-sialylated oligosaccharides,a highly efficient one-pot three-enzyme synthetic approach was applied.The P.multocida α2–3-sialyltransferase (PmST1) involved in the synthesis was a multifunctional enzyme with extremely flexible donor and acceptor substrate specificities.Sialyltransferase acceptors,including type 1 structure (Galβ1–3GlcNAcβProN3),type 2 structures (Galβ1–4GlcNAcβProN3 and 6-sulfo-Galβ1– 4GlcNAcβProN3),type 4 structure (Galβ1–3GalNAcβProN3),type 3 or core 1 structure (Galβ1–3GalNAcβProN3) and human milk oligoscaccharide or lipooligosaccharide lacto-N-tetraose (LNT) (Galβ1–3GlcNAcβ1–3Galβ1–4GlcβProN3),were chemically synthesized.They were then used in one-pot three-enzyme reactions with sialic acid precursor ManNAc or ManNGc,to synthesize a library of naturally occurring β2–3-linked sialosides with different internal sugar structures.The sialylated oligosaccharides obtained are valuable probes for their biological studies.展开更多
基金The National Key R&D Program of China(Grant No.2018YFA0507602)Project of National Science and Technology Major Project(Grant No.2019ZX09301-106)the National Natural Science Foundation of China(Grant No.91853122).
文摘A series of carbamate-containing sialyltransferase inhibitors were designed and synthesized to simulate phosphate-linked CMP-Neu5Ac.Their inhibitory activities were assayed against recombinant human ST3Gal I and ST6Gal I by using the Schmidt’s HPLC-based assay.The synthetic compound 15 g showed moderate inhibitory activity.These findings implied that carbamate might serve as a bioisosteric replacement for a phosphate group in sialyltransferase inhibitor design to improve the membrane permeability.
文摘BACKGROUND: The incidence of extrahepatic bile duct carcinoma (EBDC) has been increasing, especially in aged people, but the glycobiology of the tumor is not elucida- ted. In this study we investigated the expressions of three glycosyltransferases in 35 patients with EBDC and 35 pa- tients with benign biliary duct disease (BBDD) as well as their clinicopathological significance. METHOD: The patients were divided into several sub- groups by tumor differentiation, TNM stage, and invasion by the standards recommended by UICC. Tumor samples were immediately frozen in liquid nitrogen after resection, followed by mRNA determination of enzymes in the tissue using a mRNA selective reverse trancriptase-polymerase chain reaction kit. The mRNA levels of different groups were semi-quantitatively compared. RESULTS: The mRNA levels of N-acetylglucosaminyltrans- ferase V (GnT-V) and a subtype of α2,3 sialyltransferases for N-glycans, ST3Gal- were elevated 7.75 and 5.39 times in EBDC as compared with BBDD, respectively, and they were correlated to several clinicopathological factors including tumor advancement, differentiation, metastasis, and invasiveness. The mRNA expression of another sialyl- transferase, ST6Gal- , was also 0.63-fold higher in EBDC than in BBDD, but not involved in the clinicopathological characteristics. CONCLUSION: The elevated expression of these three gly- cosyltransferases can be considered as an important molecu- lar event in the occurrence and progression of EBDC.
基金supported by NIH grants R01GM076360 and U01CA128442
文摘Sialic acids are common terminal carbohydrates on cell surface.Together with internal carbohydrate structures,they play important roles in many physiological and pathological processes.In order to obtain α2–3-sialylated oligosaccharides,a highly efficient one-pot three-enzyme synthetic approach was applied.The P.multocida α2–3-sialyltransferase (PmST1) involved in the synthesis was a multifunctional enzyme with extremely flexible donor and acceptor substrate specificities.Sialyltransferase acceptors,including type 1 structure (Galβ1–3GlcNAcβProN3),type 2 structures (Galβ1–4GlcNAcβProN3 and 6-sulfo-Galβ1– 4GlcNAcβProN3),type 4 structure (Galβ1–3GalNAcβProN3),type 3 or core 1 structure (Galβ1–3GalNAcβProN3) and human milk oligoscaccharide or lipooligosaccharide lacto-N-tetraose (LNT) (Galβ1–3GlcNAcβ1–3Galβ1–4GlcβProN3),were chemically synthesized.They were then used in one-pot three-enzyme reactions with sialic acid precursor ManNAc or ManNGc,to synthesize a library of naturally occurring β2–3-linked sialosides with different internal sugar structures.The sialylated oligosaccharides obtained are valuable probes for their biological studies.
