Affinity-guided protein conjugation: the trilogy of covalent protein labeling, assembly and inhibition
Publication in refereed journal

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其它資訊
摘要Specific and dynamic biological interactions pave the blueprint of signal networks in cell. For example, a great variety of specific protein-ligand interactions define how intracellular signals flow. Taking advantage of the specificity of these interactions, we postulate an “affinity-guided covalent conjugation” strategy to lock binding ligands through covalent reactions between the ligand and the receptor protein. The presence of a nucleophile close to the ligand binding site of a protein is sine qua none of this reaction. Specific noncovalent interaction of a ligand derivative (which contains an electrophile at a designed position) to the ligand binding site of the protein brings the electrophile to the close proximity of the nucleophile. Subsequently, a conjugation reaction spontaneously takes place between the nucleophile and the electrophile, and leads to an intermolecular covalent linkage. This strategy was first showcased in coiled coil peptides which include a cysteine mutation at a selected position. The short peptide sequence was used for covalent labeling of cell surface receptors. The same strategy was then used to guide the design of a set of protein Lego bricks for covalent assembly of protein complexes of unnatural geometry. We finally made “reactive peptides” for natural adaptor proteins that play significant roles in signal transduction. The peptides were designed to react with a single domain of the multidomain adaptor protein, delivered into the cytosol of neurons, and re-directed the intracellular signal of neuronal migration. The trilogy of protein labeling, assembly, and inhibition of intracellular signals, all through a specific covalent bond, fully demonstrated the generality and versatility of “affinity-guided covalent conjugation” in various applications.
著者Yu Y., Xia J.
期刊名稱Science China Chemistry
詳細描述2016.
出版年份2016
月份7
日期1
卷號59
期次7
出版社Zhongguo Kexue Zazhishe/Science in China Press
出版地China
頁次853 - 861
國際標準期刊號1674-7291
電子國際標準期刊號1869-1870
語言英式英語
關鍵詞affinity-guided reaction, bioconjugation reaction, covalent labeling, inhibitor, peptide-peptide interaction, protein assembly, signal transduction

上次更新時間 2020-19-10 於 02:54