Genetically Encoding Fluorosulfate-l-tyrosine To React with Lysine, Histidine, and Tyrosine via SuFEx in Proteins in Vivo

• DOI: 10.1021/jacs.8b01087
• Publication Date: 2018-03-30T19:30:59Z
• Authors: Nanxi Wang; Bing Yang; Caiyun Fu; He Zhu; Feng Zheng; Tomonori Kobayashi; Jun Liu; Shanshan Li; Cheng Ma; Peng G. Wang; Qian Wang; Lei Wang
• Keywords: Protein Engineering; Reactivity; Chemical Biology

Introducing new chemical reactivity into proteins in living cells would endow innovative covalent bonding ability to for research and engineering vivo. Latent bioreactive unnatural amino acids (Uaas) can be incorporated react with target natural acid residues via proximity-enabled reactivity. To expand the diversity of amenable such vivo, a functionality that is biocompatible able multiple under physiological conditions highly desirable. Here we report genetic encoding fluorosulfate-l-tyrosine (FSY), first latent Uaa undergoes sulfur-fluoride exchange (SuFEx) on FSY was found nontoxic Escherichia coli mammalian cells; after being proteins, it selectively reacted proximal lysine, histidine, tyrosine SuFEx, generating intraprotein bridge interprotein cross-link interacting directly cells. The proximity-activatable reactivity, multitargeting ability, excellent biocompatibility will invaluable manipulation Moreover, genetically encoded hereby empowers general next generation click chemistry, which afford broad utilities biology, drug discovery, biotherapeutics.