Synthesis of bioactive amino acid building blocks and their applications towards the peptides and glycopeptides

• Main Author: Pasunooti, Kalyan Kumar
• Other Authors: Liu Xuewei
• Format: Theses and Dissertations
• Language: English
• Published: 2011
• Subjects: DRNTU::Science::Chemistry::Biochemistry
• Online Access: https://hdl.handle.net/10356/46460
• Institution: Nanyang Technological University

Since the discovery of native chemical ligation (NCL) by Kent and coworkers in 1994, the field of peptide synthesis has been achieved significant advancement over the last two decades. This study demonstrated that the reaction undergoes a chemoselective ligation with unprotected peptides and proteins. Inspired by Dawson’s NCL followed by desulfurization strategy, several other research groups explored the native chemical ligation concept. In 2007, Crich and co-workers demonstrated “native chemical ligation at Phenylalanine”. Considerable efforts have been made on extending the applicability of NCL on various amino acid residues. Another successful native chemical ligation/desulfurization strategy was demonstrated on Valine by Seitz and Danishefsky groups in 2008. These two groups extended the scope of the native chemical ligation strategy using thiol containing Valine as a sulfur source. Based on previous investigations, we successfully synthesized lysine building blocks and expanded NCL concept to lysine and expanded application to synthesize ubiqutin and diubiquitin proteins. Further, we are extending the NCL strategy to aspartic acid (Asp) residue which can be utilized in N-linked glycopeptide synthesis. These N-linked glycopeptides are useful building blocks for glycopeptide-based vaccines (HIV-1 entry inhibitor). We have chosen a new synthetic strategy which combines the benefits of SPPS and convergent on-resin peptide synthesis to N-glycopeptides. Conventional synthetic approaches to N-glycopeptides lengthy and inefficient.