University of 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.
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.