Two bridged purine dinucleosides, bis(2-N-acetyl-6-N-alkylylene-2,6-diaminopurine-2',3',5'-triacetyl-beta-D-ribofuranoside), were synthesized fi om the reaction of the key medium 3, 2-acetylamino-6-[1-(1,2...Two bridged purine dinucleosides, bis(2-N-acetyl-6-N-alkylylene-2,6-diaminopurine-2',3',5'-triacetyl-beta-D-ribofuranoside), were synthesized fi om the reaction of the key medium 3, 2-acetylamino-6-[1-(1,2,4-triazolyl)]-purine-2',3',5'-triacetyl-beta-D-ribofuranoside with dialkylamine.展开更多
Reaction of 5'-O-p-methoxytritylthymidine with 1,1'-carbonyl-diimidazole gave the 3'-O-carbonylimidazolide, which was condensed in high yield with 3'-O-protected thymidine to give a dinucleoside carbon...Reaction of 5'-O-p-methoxytritylthymidine with 1,1'-carbonyl-diimidazole gave the 3'-O-carbonylimidazolide, which was condensed in high yield with 3'-O-protected thymidine to give a dinucleoside carbonate. In the synthesis of dinucleoside carbonate, allyl can be used as a good protecting group for 3'-hydroxyl of thymidine. The condition of deprotection will not affect the carbonate bridges.展开更多
A series of novel dinucleosides linked by s-triazine were synthesized via the nucleophilic substitution reaction of amino nucleoside and cyanuric chloride in THF/H20. The biological activities of these novel dinucleos...A series of novel dinucleosides linked by s-triazine were synthesized via the nucleophilic substitution reaction of amino nucleoside and cyanuric chloride in THF/H20. The biological activities of these novel dinucleoside analogs against HIV-RT, HeLa and A-549 cell lines in vitro were evaluated.展开更多
A novel and efficient method for the preparation of nucleoside 5＇-tetraphosphates has been developed by coupling nucleoside 5＇-phosphoropiperidates with triphosphate reagent in the presence of 4, 5-dicyanoimidazole ...A novel and efficient method for the preparation of nucleoside 5＇-tetraphosphates has been developed by coupling nucleoside 5＇-phosphoropiperidates with triphosphate reagent in the presence of 4, 5-dicyanoimidazole （DCI） activator. Further coupling of the nucleoside 5＇-tetraphosphates with nucleoside 5＇-phosphoropiperidates via the P（V）-N activation strategy provided a reliable synthetic method for both symmetrical and asymmetrical dinucleoside pentaphosphates.展开更多
The ubiquitin-activating enzyme E1 (EC 6.3.2.19) represents the first step in the degradation of proteins by the ubiquitin proteasome pathway. E1 transfers ubiquitin from the ubiquitinated E1 to the ubiquitin carrier ...The ubiquitin-activating enzyme E1 (EC 6.3.2.19) represents the first step in the degradation of proteins by the ubiquitin proteasome pathway. E1 transfers ubiquitin from the ubiquitinated E1 to the ubiquitin carrier proteins (E2), ubiquitin-protein ligases (E3) and proteins. This process is rather complex, and known from the work of Haas, Ciechanover, Hershko, Rose and others. The occurrence of 19 hypothetical intermediate enzyme forms (EFs) and 22 different reactions were considered in the presence of ubiquitin (Ub), ATP, adenosine 5’-tetraphosphate (p4A), pyrophosphate (P2), and tripolyphosphate (P3) as substrates, and iodoacetamide (IAA) and dithioth- reitol (DTT) as inhibitors. Inspired by the work of Cha (Cha (1968) J. Biol. Chem., 243, 820-825) we have treated these reactions in two complementary ways: in rapid equilibrium and in steady state. The kinetics of both types of reactions were simulated and solved with a system of ordinary differential equations using the Mathematica Program. The ubiquitination of E1 has been also theoretically coupled to the ubiquitination of E2, E3 and proteins. This makes the model useful to predict the theoretical influence of inhibitors (or of changes in some parameters of the reaction) on the ubiquitination of proteins. The Program responds to changes in the concentration of ATP or ubiquitin and has predictive properties as shown by the influence of AMP on the synthesis of p4A, calculated theoretically and confirmed experimentally.展开更多
文摘Two bridged purine dinucleosides, bis(2-N-acetyl-6-N-alkylylene-2,6-diaminopurine-2',3',5'-triacetyl-beta-D-ribofuranoside), were synthesized fi om the reaction of the key medium 3, 2-acetylamino-6-[1-(1,2,4-triazolyl)]-purine-2',3',5'-triacetyl-beta-D-ribofuranoside with dialkylamine.
文摘Reaction of 5'-O-p-methoxytritylthymidine with 1,1'-carbonyl-diimidazole gave the 3'-O-carbonylimidazolide, which was condensed in high yield with 3'-O-protected thymidine to give a dinucleoside carbonate. In the synthesis of dinucleoside carbonate, allyl can be used as a good protecting group for 3'-hydroxyl of thymidine. The condition of deprotection will not affect the carbonate bridges.
基金Projected supported by the National Basic Research 973 Pre-research Program of China （No. 2010CB534913）, the National Natural Science Foundations of China （NSFC） （Nos. 20672027 and 20972039）, the Natural Science Foundations of Hebei Province （No. B2008000588） and the program of Science and Technology （S ＆ T） of Hebei Province （No. 09276418D-13）.
文摘A series of novel dinucleosides linked by s-triazine were synthesized via the nucleophilic substitution reaction of amino nucleoside and cyanuric chloride in THF/H20. The biological activities of these novel dinucleoside analogs against HIV-RT, HeLa and A-549 cell lines in vitro were evaluated.
基金the National Natural Science Foundation of China(Nos.21002041 and 21262014)Key Project of Chinese Ministry of Education(No.212092)+1 种基金Scientific Research Foundation of Chinese Ministry of Human Resources and Social Security for Returned Chinese Scholars(2011),and Research Funds(Nos.ky2012zy08 and 2013QNBJRC001)Startup Funds for PhDs(2010)from JXSTNU for financial support
文摘A novel and efficient method for the preparation of nucleoside 5＇-tetraphosphates has been developed by coupling nucleoside 5＇-phosphoropiperidates with triphosphate reagent in the presence of 4, 5-dicyanoimidazole （DCI） activator. Further coupling of the nucleoside 5＇-tetraphosphates with nucleoside 5＇-phosphoropiperidates via the P（V）-N activation strategy provided a reliable synthetic method for both symmetrical and asymmetrical dinucleoside pentaphosphates.
文摘The ubiquitin-activating enzyme E1 (EC 6.3.2.19) represents the first step in the degradation of proteins by the ubiquitin proteasome pathway. E1 transfers ubiquitin from the ubiquitinated E1 to the ubiquitin carrier proteins (E2), ubiquitin-protein ligases (E3) and proteins. This process is rather complex, and known from the work of Haas, Ciechanover, Hershko, Rose and others. The occurrence of 19 hypothetical intermediate enzyme forms (EFs) and 22 different reactions were considered in the presence of ubiquitin (Ub), ATP, adenosine 5’-tetraphosphate (p4A), pyrophosphate (P2), and tripolyphosphate (P3) as substrates, and iodoacetamide (IAA) and dithioth- reitol (DTT) as inhibitors. Inspired by the work of Cha (Cha (1968) J. Biol. Chem., 243, 820-825) we have treated these reactions in two complementary ways: in rapid equilibrium and in steady state. The kinetics of both types of reactions were simulated and solved with a system of ordinary differential equations using the Mathematica Program. The ubiquitination of E1 has been also theoretically coupled to the ubiquitination of E2, E3 and proteins. This makes the model useful to predict the theoretical influence of inhibitors (or of changes in some parameters of the reaction) on the ubiquitination of proteins. The Program responds to changes in the concentration of ATP or ubiquitin and has predictive properties as shown by the influence of AMP on the synthesis of p4A, calculated theoretically and confirmed experimentally.
