Wang Peng’s team from Southern University of Science and Technology School of Medicine has made new breakthroughs in glycopeptide synthesis research 2021
Glycopeptides are macromolecular compounds that combine oligosaccharides and polypeptides. Glycopeptides have very important applications in the development of carbohydrate drugs such as glycopeptide antibiotics and anti-tumor vaccines. After decades of development, peptide synthesis technology is now very mature, and the synthesis of oligosaccharides has also made important progress in recent years. However, the synthesis of glycopeptides is still a very challenging problem. Recently, Angew.
Chem. Int. Ed. published an online paper entitled: Machine Driven Chemoenzymatic Synthesis of Glycopeptide, which was completed by the Wen Liuqing research group of Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Professor Wang Peng of Southern University of Science and Technology.
This study reported for the first time the use of commercial peptide synthesizers and chemical enzymatic synthesis strategies to synthesize glycopeptides with complex oligosaccharide structures (Proof of Concept).
In this study, the author screened a large number of solid-phase supports that can be used for solid-phase synthesis, and finally found a silicon sphere with aminated surface, which can be used for both organic phase peptide synthesis and aqueous phase oligosaccharides. Synthesis (enzyme reaction).
This kind of silicon ball only has amino groups on the surface, so the author designed a cleavable linker to connect the silicon ball resin with the starting amino acid. Although the loading efficiency of this silica ball resin is lower than the commonly used solid-phase resin for peptide synthesis, it can support both the peptide synthesis reaction in the organic phase and the enzyme-catalyzed reaction in the water phase.
Based on this, researchers combined with a commercial peptide synthesizer to develop a two-phase reaction system for glycopeptide synthesis technology platform. The resin loaded with the initial amino acid is added to the reactor in advance, and then the synthesizer automatically adds the next amino acid and the condensation reagent (deprotection reagent) to the reactor. After the reaction is completed, the remaining reagents are filtered under pressure to complete a cycle.
The basic principle of automatic synthesis of glycopeptides by chemical enzymatic method. By setting the reaction program, the corresponding amino acids can be cyclically reacted in sequence, and the target peptide chain can be obtained after multiple cycles.
After that, the system is switched to the water phase, and different glycosyltransferases and corresponding glyconucleosides are sequentially subjected to the same cyclic reaction (reaction temperature is 37 ℃). After multiple cycles, the target glycopeptide can be obtained, and then the glycopeptide Elute from the resin. The glycopeptide synthesis platform is simple and easy to operate.
For the first time, a commercial peptide synthesizer has been used to realize the semi-automatic synthesis of 13 complex glycopeptides (10 tumor markers MUC1 glycopeptides and three HIV glycopeptides). Researcher Wen Liuqing of Shanghai Institute of Materia Medica and Professor Wang Peng of Southern University of Science and Technology are the co-corresponding authors of the paper; Dr. Jiabin Zhang and Dr. Ding Liu are the co-first authors of the paper. The project was supported by the NIH Common Fund Glycoscience program of the United States and the talent start-up funding of the Shanghai Institute of Medicine.
Introduction of Professor Wang Peng:
Wang Peng, Chair Professor of School of Medicine, Southern University of Science and Technology, returned to China full-time to join SUSTech in 2019; the winner of the Claude S. Hudson Award, the highest award in the U.S. glycochemistry industry in 2021, is the first scholar born in mainland China to receive this award ; American AAAS Fellow; Distinguished Professor of the Ministry of Education and Foundation Committee Jie Qing (overseas);
Bachelor of Science in Chemistry from Nankai University in 1984, Ph.D. in Organic/Bioorganic Chemistry from University of California, Berkeley in 1990, University of California, Berkeley and Scribe Postdoctoral Fellow at the Puth Institute; Assistant Professor, Department of Chemistry, University of Miami, Full Professor and Tenured Professor, Department of Chemistry, Wayne State University, United States, Chair Professor, Department of Biochemistry and Chemistry, Ohio State University, United States, Chair Professor, Department of Chemistry, Georgia State University, United States, Dean of the School of Pharmacy of Nankai University, China.
He once established the National Sugar Engineering Technology Research Center and served as the director of the Sugar Center; he has undertaken a number of scientific research projects in China and the United States; has 8 invention patents, participated in the compilation of 7 academic monographs, and is international More than 440 papers have been published in academic journals, with H-index 57 (Google Scholar) and 47 (Web of Science). He is the associate editor or editorial board member of many international academic journals, leading the team to engage in basic scientific research in single-cell glycobiology, glycochemistry, medicinal chemistry, chemical biology, glycoproteomics, and RNA drugs and antibody drugs. Research and development.