한빛사논문
- 조회1,544
Abstract
Jennifer L. Furman †§, Mingchao Kang †‡§, Seihyun Choi †, Yu Cao †, Erik D. Wold †, Sophie B. Sun †‡, Vaughn V. Smider †, Peter G. Schultz *†‡, and Chan Hyuk Kim *‡
† Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States
‡ California Institute for Biomedical Research, 11119 North Torrey Pines Road Suite 100, La Jolla, California 92037, United States
*Corresponding Authors
§These authors contributed equally.
Abstract
Selective covalent bond formation at a protein-protein interface potentially can be achieved by genetically introducing into a protein an appropriately “tuned” electrophilic unnatural amino acid that reacts with a native nucleophilic residue in its cognate receptor upon complex formation. We have evolved orthogonal aminoacyl-tRNA synthetase/tRNACUA pairs that genetically encode three aza-Michael acceptor amino acids, Nε-acryloyl-(S)-lysine (AcrK, 1), p-acrylamido-(S)-phenylalanine (AcrF, 2), and p-vinylsulfonamido-(S)-phenylalanine (VSF, 3), in response to the amber stop codon in Escherichia coli. Using an αErbB2 Fab-ErbB2 antibody-receptor pair as an example, we demonstrate covalent bond formation between an αErbB2-VSF mutant and a specific surface lysine ε-amino group of ErbB2, leading to near quantitative cross-linking to either purified ErbB2 in vitro or to native cellular ErbB2 at physiological pH. This efficient biocompatible reaction may be useful for creating novel cell biological probes, diagnostics, or therapeutics that selectively and irreversibly bind a target protein in vitro or in living cells.
논문정보
- Research article
- 2014년 05월 (BRIC 등록일 2014-06-03)
- 국외 연구진
댓글 작성 로그인
팝업 닫기관련 링크
