at Peking University School of Pharmaceutical Sciences
​​​​the dong research group

Voltage Imaging

Welcome to Dong Research Group!
Protein-based biomacromolecules have been broadly studied for their essential roles in organisms. An important strategy for protein production is chemical peptide synthesis, in which native chemical ligation (NCL) is one of the most powerful and frequently used methods employed. Although the scope of the ligation sites has been widely brodened after the development of metal-free desulfurization (MFD), the diversity of peptide sequences still arouses an urge for scientists to explore new ligation methods for protein chemical synthesis.

As for the bulky amino acid sites (e.g. Pro, Val, Ile, etc.) at C-termini, their reaction rates are constrained, limiting the relevant peptide synthesis. In the past, sulfydryl within the peptide segments to activate the C-termini under thiol additive-free conditions has been greatly exploited. Based on this, we have developed mild and efficient internal activation protocols of peptidyl prolyl thioesters and valinyl benzimidazolinones in NCL, which respectively improve the ligation efficiency at the Pro-Xaa sites and Val-Xaa sites. For the prolyl thioesters, the introduction of a 4-mercaptan substituent improves the reactivity via the formation of a bicyclic thiolactone intermediate. Benifiting from the ring strain, the ligtion could go smoothly with high efficiency. Based on the same concept, the efficiency of the liagation at the Val-Xaa sites was increased by the generation of thiolactone form penicillamine derived precusor. 
More recently, we developed a traceless β-mercaptan-assisted α-selective ligation of  N-terminal lysine-containing peptides. In this ligation-desulfurization-based protocol, the -amine of lysine is not capped and requires for less deprotection steps, thus improving the overall synthetic efficiency and avoiding harsh reaction condtions.