Site Selective Azo Coupling for Peptide Cyclization and Affinity Labeling of an SH3 Protein
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AbstractA key challenge in bioconjugation is to control the site selectivity of the reaction. Chemical reagents often react with proteineous chemical groups without showing preference to their location or microenvironment in the protein; to confine the reaction to an amino acid at a specific site, one needs to distinguish this residue from others despite their identical chemical properties. Here, we report a strategy that utilizes proximity-driven reactivity to achieve site selective azo coupling between tyrosine and aryldiazonium. A phenylalanine analogue with an aryldiazonium moiety at its side chain was incorporated into a synthetic peptide and was found to react only with tyrosine in its vicinity but also to remain inert to others that are not immediately adjacent, a property attained by fine regulation of the electronic effect of the substituent on the aryl ring. Proximity-driven intramolecular azo coupling was showcased in cyclization of a beta-hairpin peptide, structural features of the azo linked cyclic peptide was elucidated by NMR, and intermolecular azo coupling was achieved between an SH3 protein Abl-SH3 and its polyproline peptide ligands at specific tyrosine residues. This approach is generally applicable to develop covalent affinity labels for SH3 proteins because of the high occurrence rate of tyrosine at the peptide-binding site of SH3 proteins.
All Author(s) ListHuang F, Nie YY, Ye F, Zhang MJ, Xia J
Journal nameBioconjugate Chemistry
Detailed descriptionDOI: 10.1021/acs.bioconjchem.5b00238.
Year2015
Month8
Day1
Volume Number26
Issue Number8
PublisherAMER CHEMICAL SOC
Pages1613 - 1622
ISSN1043-1802
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesBiochemical Research Methods; Biochemistry & Molecular Biology; Chemistry; Chemistry, Multidisciplinary; Chemistry, Organic

Last updated on 2020-25-11 at 00:08