Date | 06 Feb 2025 |
Time | 2:00 pm - 3:00 pm (HKT) |
Venue | Lecture Theatre T7, Meng Wah Complex |
Speaker | Prof. Lei LIU |
Institution | Department of Chemistry, Tsinghua University |

Title:
Chemical synthesis of human proteoforms
Schedule:
Date: 6th February, 2025 (Thursday)
Time: 2 - 3 pm (HKT)
Venue: Lecture Theatre T3, Meng Wah Complex
Speaker:
Prof. Lei LIU
Department of Chemistry
Tsinghua University
Biography:
Prof. Lei Liu graduated from University of Science and Technology of China (1999). He obtained the Ph.D. degree from Columbia University (2004), followed by the post-doctorial research work at Scripps Research Institute (2004-2007). He has joined Tsinghua University since 2007, employed as a professor in the Chemistry Department. His research interest is synthetic bioorganic chemistry with two directions: 1. chemical synthesis and modification of proteins; 2. catalytic synthesis of bioactive small molecules.
Abstract:
Inadequate understanding of the functions and mechanisms of human proteoforms carrying complex combinations of post-translational modifications remains an obstacle to the study of human health and disease. These proteoforms are difficult to produce in homogeneous forms using traditional biotechnologies such as recombinant expression, while chemical protein synthesis enables the generation of human proteoforms with defined structures at chemical precision. Through the past years our team has been working on the development of a comprehensive, robust, and cost-effective methodology for the chemical synthesis of all human proteoforms, which has entailed three strategies: 1) easy-to-use peptide ligation chemistries that allow for more efficient de novo synthesis of any protein structural domains; 2) robust strategies for providing temporary structural support for the ligation and folding of more challenging protein targets; and 3) efficient transpeptidative protein domain/domain ligation methods for the synthesis of multi-domain proteins. Through successful chemical synthesis of more human proteoforms and use of them in biomedical research, our team has also increasingly appreciated the genuine usefulness of chemical protein synthesis in the following areas: 1) profiling and biochemical reconstitution of human proteoform interaction networks, 2) structural mechanism elucidation and functional analysis of human proteoform complexes, and 3) development and evaluation of drug candidates targeting human proteoforms. Taken together, our work indicates that through integration with in vivo functional analysis, mechanistic biochemistry, and drug development, chemical protein synthesis can play an important role in deciphering human health and disease and facilitates the development of precision diagnostics and therapeutics.
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