Solid phase peptide synthesis(SPPS)based on Fmoc chemistry has become a commonly used technique in peptide chemistry,as it can be easily conducted using automated machine,and not requiring highly toxic HF in compariso...Solid phase peptide synthesis(SPPS)based on Fmoc chemistry has become a commonly used technique in peptide chemistry,as it can be easily conducted using automated machine,and not requiring highly toxic HF in comparison to Boc-SPPS.With the fast development in the emerging field of protein chemical synthesis,many efforts have been endeavored aiming to find more efficient methods for preparing peptide fragments required in ligation reactions.This review briefly summarizes recent advances in the engineering and modification of Fmoc-SPPS-derived peptides,which can be used as the N-terminal fragments in a native chemical ligation(NCL)or NCL-type ligation reactions.展开更多
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
基金supported by the Peking University Health Science Center(BMU20130354)State Key Laboratory of Natural and Biomimetic Drugs,the National Recruitment Program of Global Youth Experts(1000 Plan)the National Natural Science Foundation of China (21502005)
文摘Solid phase peptide synthesis(SPPS)based on Fmoc chemistry has become a commonly used technique in peptide chemistry,as it can be easily conducted using automated machine,and not requiring highly toxic HF in comparison to Boc-SPPS.With the fast development in the emerging field of protein chemical synthesis,many efforts have been endeavored aiming to find more efficient methods for preparing peptide fragments required in ligation reactions.This review briefly summarizes recent advances in the engineering and modification of Fmoc-SPPS-derived peptides,which can be used as the N-terminal fragments in a native chemical ligation(NCL)or NCL-type ligation reactions.
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.
