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 (pAC), 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 pAC 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 pAC 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/pAC complex.

Tommasone, S., Talotta, C., Gaeta, C., Margarucci, L., Monti, M., Casapullo, A., et al. (2015). Biomolecular Fishing for Calixarene Partners by a Chemoproteomic Approach. ANGEWANDTE CHEMIE. INTERNATIONAL EDITION, 54, 15405-15409 [10.1002/anie.201508651].

Biomolecular Fishing for Calixarene Partners by a Chemoproteomic Approach

MACCHI, BEATRICE;PRETE, SALVATORE;
2015

Abstract

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 (pAC), 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 pAC 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 pAC 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/pAC complex.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore CHIM/03 - Chimica Generale e Inorganica
Settore BIO/14
English
Con Impact Factor ISI
biomolecular recognition; calixarenes; chemical proteomics; proteins; surface plasmon resonance
Tommasone, S., Talotta, C., Gaeta, C., Margarucci, L., Monti, M., Casapullo, A., et al. (2015). Biomolecular Fishing for Calixarene Partners by a Chemoproteomic Approach. ANGEWANDTE CHEMIE. INTERNATIONAL EDITION, 54, 15405-15409 [10.1002/anie.201508651].
Tommasone, S; Talotta, C; Gaeta, C; Margarucci, L; Monti, M; Casapullo, A; Macchi, B; Prete, S; Ladeira De Araujo, A; Neri, P
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/132883
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