Water-enhanced chemoselective ligation

ORGN 412

Yan-Yeung Luk, yluk@syr.edu, Preeti Sejwal, psejwal@syr.edu, and YongBin Han, yhan03@mailbox.syr.edu. Department of Chemistry; Department of Biomedical and Chemical Engineering, Syracuse University, 1-014 CST, 111 College Place, Syracuse, NY 13244
Organic reactions with high chemoselevtivity in entirely aqueous environment are tremendously useful for investigating various aspects of life sciences. In this work, we report a new reaction that proceeds in aqueous buffer with high chemoselectivity. When compared with other organic solvents, the rate of this chemoselective ligation is significantly enhanced in aqueous solution than in methanol or in DMSO. This ligation, involving exclusively N-terminus cysteine and a tailored squarate derivative, proceed with a two-step binding-substitution mechanism. This chemistry compares favorably over the commercial product of maleimide plate for immobilizing peptides or proteins, and presents potential for tracing cell signaling pathways in a living cell.