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A Peptide Stapling Strategy with Built‐In Fluorescence by Direct Late‐Stage C(sp 2 )−H Olefination of Tryptophan
Author(s) -
Liu Jiang,
Liu Xin,
Zhang Fangfang,
Qu Jiaojiao,
Sun Hongyan,
Zhu Qing
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202003548
Subject(s) - chemistry , fluorophore , peptide , tryptophan , fluorescence , combinatorial chemistry , regioselectivity , cyclic peptide , pyridine , amino acid , stereochemistry , biochemistry , catalysis , organic chemistry , physics , quantum mechanics
Fluorescent stapled peptides are important chemical tools for detecting intracellular distribution, protein–protein interactions, and localization of target proteins. These peptides are usually labeled with bulky sized fluorophores through reactive functional groups, which may alter the physical properties and biological activities of peptides. Herein, a unique strategy is developed for synthesizing new stapled peptides with built‐in fluorescence. The stapled peptides were prepared through Rh‐catalyzed C(sp 2 )−H olefination in tryptophan (Trp) residues by using pyridine/pyrimidine as the directing groups under mild conditions. This method displays good regioselectivity and high efficiency. Furthermore, as a proof of concept for its biological applications, stapled peptides without additional fluorophore 9 a and 9 b were constructed for a cell imaging study. These peptides displayed strong binding affinity toward integrin αvβ3 in A549 cells by cell imaging experiments. Notably they demonstrated even better anticancer activity than commercial antagonist cyclic (RGDfK). The method will provide robust tools for the peptide macrocyclization field.