School of Life Sciences, Westlake University
Copper-Assisted Sequence-Specific Chemical Protein Conjugation
SESSION 14: NOVEL ADVANCES IN PEPTIDE CHEMISTRY
Thursday, June 29, 2023, at 02:45 pm - 03:05 pm
Direct site-specific methods of chemical protein functionalization are highly desirable. However, such methods are particularly challenging to develop due to the tremendous difficulty of chemically differentiating the same amino acid type at different protein sites.
Herein, we proposed "metal binding targeting" strategy and developed Copper Assisted Sequence-specific conjugation Tag, CAST to achieve single site-specific protein conjugations. CAST possesses superior reaction kinetics with a rate constant of 8.1 M-1 s-1 in aqueous buffer.
Importantly, CAST conjugation can be employed as a universal method for efficient and quantitative payload attachment on different proteins. We also highlight that an antibody drug conjugate prepared using CAST is highly stable in plasma and exhibits potent efficacy in vitro and in vivo.
M. Guo, et al., Copper-Assisted Sequence-Specific Chemical Protein Conjugation
. Science. Currently under peer review, 2023.
Dr. Dang received his B.S. in School of Chemistry and Chemical Engineering at Nanjing University. He then went to the University of Chicago and obtained his Ph.D. degree in Department of Chemistry focusing on studying protein ion channel ligands, venom toxins, through chemical protein synthesis. Dr. Dang did his post-doctoral researches at Department of Pharmaceutical Chemistry, UCSF using computational protein design and biological display technologies to develop novel protein structures and technologies. Dr. Dang has published many papers in high-profile journals including Nature Methods, J. Am. Chem. Soc., Angew. Chem. Int. Ed., Neuron, and PNAS. Outside of scientific research, Dr. Dang likes rock climbing, snowboarding and hiking.