Oral Presentation 6th Modern Solid Phase Peptide Synthesis & Its Applications Symposium 2017

New tools in protein total synthesis and chemical modification (#5)

Xuechen Li 1
  1. The University of Hong Kong, Hong Kong

Protein chemical synthesis1 and modification2 provide important tools to produce chemical probes to study the function of proteins and develop therapeutic biologics. However, due to the presence of diverse functionalities of amino acid side chains in a peptide/protein sequence, development of the effective chemical methods to directly manipulate these biomacromolecules is challenging, for which mildness, robustness and chemoselectivity are essential but difficult to achieve. Chemoselective peptide ligations provide effective tools to chemically synthesize proteins that are difficult to produce by any biologically controlled methods, such as all D-proteins and proteins carrying site-specific stoichiometric post-translational modification(s) or unnatural side chains. In our efforts, we have developed Ser/Thr ligation and sequential Ser/Thr ligation to prepare proteins that carry post-translational modifications including glycosylation and phosphorylation. In addition, we developed PT ligation for amine-specific native protein bioconjugation. In this talk, I will discuss our recent developments.

  1. 1. Bondalapati, S., Jbara, M. & Brik, A. Expanding the chemical toolbox for the synthesis of large and uniquely modified proteins. Nat. Chem. 8, 407418 (2016). 2. Spicer, C. D. & Davis, B. G. Selective chemical protein modification. Nat. Commun. 5, 4740 (2014).