Chemical synthesis of peptides and proteins has evolved into an indispensable tool for chemical biology. Peptide ligation is a straightforward technique for joining two short peptide fragments together via a native pe...Chemical synthesis of peptides and proteins has evolved into an indispensable tool for chemical biology. Peptide ligation is a straightforward technique for joining two short peptide fragments together via a native peptide bond to afford a larger natural peptide or protein. However, the junction sites are limited to several specific amino acids because most peptide ligations involve participation of the side-chain functional groups of the junction-site amino acids. To overcome such intrinsic limitations, "general"peptide ligations which do not rely on the side-chain functional group have been developed. This review summarized the recent developments in peptide ligations that are independent of side-chain functional group of ligation-junction-site amino acid.展开更多
This paper reports a computational study elucidating reaction mechanism for amide bond formation from esters and amines catalyzed by acetic acid. Two optional mechanisms（namely, classic stepwise and concerted acyl su...This paper reports a computational study elucidating reaction mechanism for amide bond formation from esters and amines catalyzed by acetic acid. Two optional mechanisms（namely, classic stepwise and concerted acyl substitution mechanisms） have been studied. Calculation results establish the reaction energy profiles of both mechanisms and locate all the intermediates and transition states in both catalytic cycles. Our results propose that the concerted acyl substitution mechanism may be more likely wherein the formation of CààN bond and the cleavage of CààO bond occur concurrently without the need of rehybridization of the carbonyl carbon. This is also consistent with the fact that no significant racemization/epimerization were observed in the amide products when asymmetric esters and/or amines were used as the reactants, because concerted acyl substitution mechanism precludes the intermediacy of tetrahedral adducts and the accompanying generation/elimination of new chiral centers.Further discussion implies that the concerted acyl substitution mechanism may widely occur in related amidation reactions in the presence of different types of coupling reagents.展开更多
基金supported by the National Natural Science Foundation of China (21462023), and the Natural Science Foundation of Jiangxi Province (20143ACB20007, 20153BCB23018)
文摘Chemical synthesis of peptides and proteins has evolved into an indispensable tool for chemical biology. Peptide ligation is a straightforward technique for joining two short peptide fragments together via a native peptide bond to afford a larger natural peptide or protein. However, the junction sites are limited to several specific amino acids because most peptide ligations involve participation of the side-chain functional groups of the junction-site amino acids. To overcome such intrinsic limitations, "general"peptide ligations which do not rely on the side-chain functional group have been developed. This review summarized the recent developments in peptide ligations that are independent of side-chain functional group of ligation-junction-site amino acid.
基金supported by the National Natural Science Foundation of China (No. 21472068)Financial support from MOE & SAFEA for the 111 Project (No. B13025)is also gratefully acknowledged
文摘This paper reports a computational study elucidating reaction mechanism for amide bond formation from esters and amines catalyzed by acetic acid. Two optional mechanisms（namely, classic stepwise and concerted acyl substitution mechanisms） have been studied. Calculation results establish the reaction energy profiles of both mechanisms and locate all the intermediates and transition states in both catalytic cycles. Our results propose that the concerted acyl substitution mechanism may be more likely wherein the formation of CààN bond and the cleavage of CààO bond occur concurrently without the need of rehybridization of the carbonyl carbon. This is also consistent with the fact that no significant racemization/epimerization were observed in the amide products when asymmetric esters and/or amines were used as the reactants, because concerted acyl substitution mechanism precludes the intermediacy of tetrahedral adducts and the accompanying generation/elimination of new chiral centers.Further discussion implies that the concerted acyl substitution mechanism may widely occur in related amidation reactions in the presence of different types of coupling reagents.
