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Biomolecular Fishing for Calixarene Partners by a Chemoproteomic Approach
Author(s) -
Tommasone Stefano,
Talotta Carmen,
Gaeta Carmine,
Margarucci Luigi,
Monti Maria Chiara,
Casapullo Agostino,
Macchi Beatrice,
Prete Salvatore Pasquale,
Ladeira De Araujo Adriana,
Neri Placido
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201508651
Subject(s) - hela , linker , chemistry , surface plasmon resonance , in vitro , combinatorial chemistry , calixarene , chaperone (clinical) , docking (animal) , biochemistry , western blot , stereochemistry , biophysics , computational biology , nanotechnology , organic chemistry , biology , molecule , materials science , gene , computer science , medicine , pathology , nanoparticle , operating system , nursing
MS‐based chemical‐proteomics technology is introduced herein as a third general strategy to study the biomolecular recognition properties of given calixarene derivatives. In particular, we demonstrate that a simply designed calix[4]arene derivative 1 a bearing acetamido groups at the exo rim ( p AC), when linked to a solid support, is able to fish out a specific protein (PDI protein) from a crude extract of HeLa cells. Western blot and surface plasmon resonance studies confirmed the direct interaction between PDI and the linker‐free p AC derivative 1 b with considerable affinity, and in vitro tests showed its inhibition of PDI chaperone activity. In accordance with the role of PDI in a variety of human cancers, biological tests showed that p AC 1 b was cytotoxic and cytostatic toward CAL‐27 and PC‐3 cancer cell lines in vitro. Docking studies showed that H bonds and hydrophobic interactions contribute to the stabilization of the PDI/ p AC complex.