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Copper‐Free Huisgen Cycloaddition for the 14‐3‐3‐Templated Synthesis of Fusicoccin‐Peptide Conjugates
Author(s) -
Masuda Ryoma,
Kawasaki Yuuya,
Igawa Kazunobu,
Manabe Yoshiyuki,
Fujii Hiroshi,
Kato Nobuo,
Tomooka Katsuhiko,
Ohkanda Junko
Publication year - 2020
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.202000042
Subject(s) - cycloaddition , fusicoccin , moiety , combinatorial chemistry , chemistry , azide , peptide , conjugate , click chemistry , chemical synthesis , cell permeability , small molecule , stereochemistry , in vitro , organic chemistry , biochemistry , enzyme , mathematical analysis , mathematics , atpase , catalysis
Abstract Mid‐sized molecules have emerged as an attractive chemical space and potentially provide a robust basis for the development of synthetic agents to control intracellular protein interactions. However, the limited cell permeability and chemical tractability of such agents remain to be addressed. We envisioned that target‐templated synthesis of such mid‐sized molecules might provide a solution. Here, we exploited a copper‐free Huisgen cycloaddition for template synthesis using a peptide fragment containing a 4,8‐diazacyclononyne (DACN) moiety and an azide‐containing fusicoccin derivative in the presence or absence of recombinant 14‐3‐3ζ protein in vitro. Time‐course changes in the yield of products demonstrated that the reaction was accelerated in the presence of 14‐3‐3 and one of the regioisomers was generated predominantly, supporting the template effect.