Native chemical ligation on aspartic acid and its application towards convergent synthesis of homogeneous N-glycoprotein

• Main Author: Chai, Hua
• Other Authors: Liu Chuan Fa
• Format: Theses and Dissertations
• Language: English
• Published: 2016
• Subjects: DRNTU::Science::Chemistry::Analytical chemistry::Proteins
• Online Access: http://hdl.handle.net/10356/66214
• Institution: Nanyang Technological University

Total synthesis of native and functional proteins was almost unachievable back in the early 1990s, but thanks to Prof Kent’s development on native chemical ligation (NCL), chemical protein synthesis has become attainable. The basis of NCL technique is the chemoselective reaction between a peptide thioester with a cysteinyl peptide. The reaction takes place in aqueous buffer and produces a native peptide bond at the cysteinyl site with unprotected peptide fragments. Considering the low natural abundance of cysteine, considerable efforts have been made on extending the scope of native chemical ligation to other proteinogenic amino acids. Our group have been interested in this area for years and have successfully demonstrated a dual native chemical ligation on lysine for the synthesis of linear and branched ubiquitin and diubiquitin proteins. Based on our previous knowledge, we wish to extend the NCL strategy to aspartic acid (Asp) residue, which is the core structure for N-glycopeptides.