Xuechen Li

Xuechen Li

University of Hong Kong
Hong Kong


New Methods and Strategies for Protein Chemical Synthesis and Modifications

Over the past years, our laboratory has developed Serine/Threonine Ligation, STL, for protein chemical synthesis, in which an N-terminal serine or threonine of one unprotected peptide can ligate with a second unprotected peptide with the C-terminal salicylaldehyde ester to afford an N,O-benzylidene acetal linked peptide that upon acidolysis generates the natural peptidic Xaa-Ser/Thr linkage at the ligation site. Considering the high abundance of serine and threonine residues in natural proteins/peptides, Ser/Thr ligation will offer new options for convergent peptide and protein synthesis.

Makineni Award Winner

Our laboratory has used Ser/Thr ligation in the synthesis of cyclic peptides including daptomycin and teixobactin, and proteins including human erythrocyte acylphosphatase, MUC1 glycopeptide, glycosylated interleukin-25, phosphorylated HMGA proteins and so on.

In addition, we recently developed an unprecedentedly mild system (TCEP/NaBH3 or TCEP/LiBEt3H) for chemoselective peptide desulfurization for extending native chemical ligation-desulfurization strategy in protein chemical synthesis. This method, termed P-B desulfurization, features usage of common reagents, simplicity of operation and versatile functionality compatibility. Furthermore, this method can readily incorporate deuterium into the peptide after cysteine desulfurization.

Lecture Images

Xuechen Li presenting at APS2019 Xuechen Li presenting at APS2019 Xuechen Li presenting at APS2019