Revealing the extracellular function of HMGB1 N-terminal region acetylation assisted by a protein semi-synthesis approach

Abstract

HMGB1 (high-mobility group box 1) is a non-histone chromatin-associated protein that has been widely reported as a representative damage-associated molecular pattern (DAMP) and to play a pivotal role in proinflammatory...

Selective Peptide Cysteine Manipulation on Demand and Difficult Protein Chemical Synthesis Enabled by Controllable Acidolysis of N,S‐Benzylidene Thioacetals

“…[19,22] After treating with trifluoroacetic acid (TFA) cocktail, both NBA and NBT can be acidolyzed to produce the native peptide bond at the ligation site, albeit for NBTs much harsher conditions and longer time are required. [14] Till now both STL and CPL have been successfully applied for the chemical syntheses of various valuable peptides/proteins including immune checkpoint proteins, [23] cytokines, [24,25] nucleosome-associated proteins with PTMs, [26][27][28][29][30] antimicrobial cyclic peptides, [31][32][33][34] etc. Importantly, the generated NBA/NBT intermediate during STL/CPL becomes advantageous in challenging protein synthesis since the highly twisted structure of NBA and NBT can serve as an aggregation disruptor, which allows us to complete the first chemical synthesis of the immune checkpoint protein programmed cell death protein 1 (PD-1) extracellular domain.…”

Selective Peptide Cysteine Manipulation on Demand and Difficult Protein Chemical Synthesis Enabled by Controllable Acidolysis of N,S‐Benzylidene Thioacetals

“…[19,22] After treating with trifluoroacetic acid (TFA) cocktail, both NBA and NBT can be acidolyzed to produce the native peptide bond at the ligation site, albeit for NBTs much harsher conditions and longer time are required. [14] Till now both STL and CPL have been successfully applied for the chemical syntheses of various valuable peptides/proteins including immune checkpoint proteins, [23] cytokines, [24,25] nucleosome-associated proteins with PTMs, [26][27][28][29][30] antimicrobial cyclic peptides, [31][32][33][34] etc. Importantly, the generated NBA/NBT intermediate during STL/CPL becomes advantageous in challenging protein synthesis since the highly twisted structure of NBA and NBT can serve as an aggregation disruptor, which allows us to complete the first chemical synthesis of the immune checkpoint protein programmed cell death protein 1 (PD-1) extracellular domain.…”