Peptide thioester preparation via intramolecular O-to-S acyl transfer is a recently developed method for protein chemical synthesis through Fmoc chemistry. Theoretical calculations have been carried out to study the m...Peptide thioester preparation via intramolecular O-to-S acyl transfer is a recently developed method for protein chemical synthesis through Fmoc chemistry. Theoretical calculations have been carried out to study the mechanism for the formation of thioesters via O-to-S acyl transfer. It is found that the O-to-S acyl transfer occurs via an anionic stepwise mechanism in which the cleavage of the C-O bond is the rate-limiting step. The side reaction of hydrolysis also proceeds through an anionic stepwise process, and its rate-limiting step is the attack of the hydroxide ion on the carbonyl carbon. Increase of the chain length between the ester O atom and the S atom can increase the energy barrier of the O-to-S acyl transfer. On the other hand, substituents at the α-position of the ester can reduce the energy barrier.展开更多
Nonalcoholic fatty liver disease(NAFLD) is currently considered as the most common liver disease in Western countries,and is rapidly becoming a serious threat to public health worldwide.However,the underlying mechanis...Nonalcoholic fatty liver disease(NAFLD) is currently considered as the most common liver disease in Western countries,and is rapidly becoming a serious threat to public health worldwide.However,the underlying mechanisms leading to the development of NAFLD are still not fully understood.The ghrelin-ghrelin O-acyltransferase(GOAT) system has recently been found to play a crucial role in both the development of steatosis and its progression to nonalcoholic steatohepatitis.Ghrelin,the natural ligand of the growth hormone secretagogue receptor,is a 28-amino acid peptide possessing a unique acylation on the serine in position 3 catalyzed by GOAT.The ghrelin-GOAT system is involved in insulin resistance,lipid metabolism dysfunction,and inflammation,all of which play important roles in the pathogenesis of NAFLD.A better understanding of ghrelin-GOAT system biology led to the identification of its potential roles in NAFLD.Molecular targets modulating ghrelin-GOAT levels and the biologic effects are being studied,which provide a new insight into the pathogenesis of NAFLD.This review probes into the possible relationship between the ghrelin-GOAT system and NAFLD,and considers the potential mechanisms by which the ghrelin-GOAT system brings about insulin resistance and other aspects concerning NAFLD.展开更多
Acyl chloride can efficiently be converted into anhydride under solid liquid phase transfer catalysis by using bis(triphenylphosphine)cobalt dichloride or bis(triphenylphospine)palladium dichloride as the catalyst.
A simple and general method for the synthesis of bi(acyl)disulfides is reported.Sulfur is allowed to react with sodium hydroxide to give sodium disulfide at 65℃ under PTC,which can react with acyl halides to afford b...A simple and general method for the synthesis of bi(acyl)disulfides is reported.Sulfur is allowed to react with sodium hydroxide to give sodium disulfide at 65℃ under PTC,which can react with acyl halides to afford bi(acyl)disulfides in good to excellent isolated yields.The effects of solvents and phase transfer catalysts are discussed.展开更多
The reactions of 5-methyl-3-hydroxyisoxazole with 2, 2-dimethyl, 3-substituted cyclopropanecarboxylic chlorides give O-acyl-5-methyl-3-hydroxyisoxazole and N-acyl-5-methylisoxazolin-3-one derivatives. The ratio of O-a...The reactions of 5-methyl-3-hydroxyisoxazole with 2, 2-dimethyl, 3-substituted cyclopropanecarboxylic chlorides give O-acyl-5-methyl-3-hydroxyisoxazole and N-acyl-5-methylisoxazolin-3-one derivatives. The ratio of O-acyl to N-acyl product depends upon the acylation reagents. O-acyl derivatives can be converted to the N-acyl compounds by isomerization under acidic conditions or heating.展开更多
基金support to the study by the National Natural Science Foundation of China (20932006)
文摘Peptide thioester preparation via intramolecular O-to-S acyl transfer is a recently developed method for protein chemical synthesis through Fmoc chemistry. Theoretical calculations have been carried out to study the mechanism for the formation of thioesters via O-to-S acyl transfer. It is found that the O-to-S acyl transfer occurs via an anionic stepwise mechanism in which the cleavage of the C-O bond is the rate-limiting step. The side reaction of hydrolysis also proceeds through an anionic stepwise process, and its rate-limiting step is the attack of the hydroxide ion on the carbonyl carbon. Increase of the chain length between the ester O atom and the S atom can increase the energy barrier of the O-to-S acyl transfer. On the other hand, substituents at the α-position of the ester can reduce the energy barrier.
基金Supported by a research grant for Key Clinical Discipline Construction of Shanghai Municipality,China,No.ZK2012B20
文摘Nonalcoholic fatty liver disease(NAFLD) is currently considered as the most common liver disease in Western countries,and is rapidly becoming a serious threat to public health worldwide.However,the underlying mechanisms leading to the development of NAFLD are still not fully understood.The ghrelin-ghrelin O-acyltransferase(GOAT) system has recently been found to play a crucial role in both the development of steatosis and its progression to nonalcoholic steatohepatitis.Ghrelin,the natural ligand of the growth hormone secretagogue receptor,is a 28-amino acid peptide possessing a unique acylation on the serine in position 3 catalyzed by GOAT.The ghrelin-GOAT system is involved in insulin resistance,lipid metabolism dysfunction,and inflammation,all of which play important roles in the pathogenesis of NAFLD.A better understanding of ghrelin-GOAT system biology led to the identification of its potential roles in NAFLD.Molecular targets modulating ghrelin-GOAT levels and the biologic effects are being studied,which provide a new insight into the pathogenesis of NAFLD.This review probes into the possible relationship between the ghrelin-GOAT system and NAFLD,and considers the potential mechanisms by which the ghrelin-GOAT system brings about insulin resistance and other aspects concerning NAFLD.
文摘Acyl chloride can efficiently be converted into anhydride under solid liquid phase transfer catalysis by using bis(triphenylphosphine)cobalt dichloride or bis(triphenylphospine)palladium dichloride as the catalyst.
文摘A simple and general method for the synthesis of bi(acyl)disulfides is reported.Sulfur is allowed to react with sodium hydroxide to give sodium disulfide at 65℃ under PTC,which can react with acyl halides to afford bi(acyl)disulfides in good to excellent isolated yields.The effects of solvents and phase transfer catalysts are discussed.
基金Supposed by the National Natural Science Foundation of China
文摘The reactions of 5-methyl-3-hydroxyisoxazole with 2, 2-dimethyl, 3-substituted cyclopropanecarboxylic chlorides give O-acyl-5-methyl-3-hydroxyisoxazole and N-acyl-5-methylisoxazolin-3-one derivatives. The ratio of O-acyl to N-acyl product depends upon the acylation reagents. O-acyl derivatives can be converted to the N-acyl compounds by isomerization under acidic conditions or heating.
