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11 results on '"Gandini, Tommaso"'

2. Innovative On‐Resin and in Solution Peptidomimetics Synthesis via Metal‐Free Photocatalytic Approach.

Author

Gandini, Tommaso, Vaghi, Francesco, Laface, Zoe, Macetti, Giovanni, Bossi, Alberto, Penconi, Marta, Luisa Gelmi, Maria, and Bucci, Raffaella

Subjects
*DRUG discovery, *AMINO acid sequence, *PEPTIDE synthesis, *PEPTIDOMIMETICS, *PEPTIDES
Abstract

Nowadays, peptidomimetics are widely studied, being useful tools in drug discovery and medicinal chemistry. The coupling between a carboxylic acid with an amine to form a peptide bond is the most common reaction to obtain peptides/peptidomimetics. In this work, we have investigated an innovative metal‐free photoredox‐catalyzed carbamoylation to form peptidomimetics thanks to the reaction between dihydropyridines functionalized with amino acids (or peptide sequences) and differently functionalized imines. As the organic photocatalyst, we used 4CzIPN, a donor‐acceptor cyanoarene vastly used in photoredox catalysis. By easily modulating the amino acid (or peptide sequence), which is directly attached to the dihydropyridine, we proposed this key‐reaction as new valuable method to obtain peptidomimetics, in situ building the not‐natural portion of the sequence. Moreover, we successfully employed this methodology in solid phase peptide synthesis, both inserting the new photoredox‐generated amino acid at the end or in the middle of the sequence. Peptides with different lengths and secondary structures were prepared, proving the success of this approach, even in sterically hindered environment. Herein, to the best of our knowledge, we describe the first photocatalytic protocol which allows the building of the peptide backbone, with the possibility of simultaneously inserting a non‐coded amino acid in the sequence. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Targeting Oncogenic Src Homology 2 Domain-Containing Phosphatase 2 (SHP2) by Inhibiting Its Protein–Protein Interactions

Author

Bobone, Sara, primary, Pannone, Luca, additional, Biondi, Barbara, additional, Solman, Maja, additional, Flex, Elisabetta, additional, Canale, Viviana Claudia, additional, Calligari, Paolo, additional, De Faveri, Chiara, additional, Gandini, Tommaso, additional, Quercioli, Andrea, additional, Torini, Giuseppe, additional, Venditti, Martina, additional, Lauri, Antonella, additional, Fasano, Giulia, additional, Hoeksma, Jelmer, additional, Santucci, Valerio, additional, Cattani, Giada, additional, Bocedi, Alessio, additional, Carpentieri, Giovanna, additional, Tirelli, Valentina, additional, Sanchez, Massimo, additional, Peggion, Cristina, additional, Formaggio, Fernando, additional, den Hertog, Jeroen, additional, Martinelli, Simone, additional, Bocchinfuso, Gianfranco, additional, Tartaglia, Marco, additional, and Stella, Lorenzo, additional

Published
2021
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8. Targeting Oncogenic Src Homology 2 Domain-Containing Phosphatase 2 (SHP2) by Inhibiting Its Protein-Protein Interactions

Author

Bobone, Sara, Pannone, Luca, Biondi, Barbara, Solman, Maja, Flex, Elisabetta, Canale, Viviana Claudia, Calligari, Paolo, De Faveri, Chiara, Gandini, Tommaso, Quercioli, Andrea, Torini, Giuseppe, Venditti, Martina, Lauri, Antonella, Fasano, Giulia, Hoeksma, Jelmer, Santucci, Valerio, Cattani, Giada, Bocedi, Alessio, Carpentieri, Giovanna, Tirelli, Valentina, Sanchez, Massimo, Peggion, Cristina, Formaggio, Fernando, den Hertog, Jeroen, Martinelli, Simone, Bocchinfuso, Gianfranco, Tartaglia, Marco, Stella, Lorenzo, Bobone, Sara, Pannone, Luca, Biondi, Barbara, Solman, Maja, Flex, Elisabetta, Canale, Viviana Claudia, Calligari, Paolo, De Faveri, Chiara, Gandini, Tommaso, Quercioli, Andrea, Torini, Giuseppe, Venditti, Martina, Lauri, Antonella, Fasano, Giulia, Hoeksma, Jelmer, Santucci, Valerio, Cattani, Giada, Bocedi, Alessio, Carpentieri, Giovanna, Tirelli, Valentina, Sanchez, Massimo, Peggion, Cristina, Formaggio, Fernando, den Hertog, Jeroen, Martinelli, Simone, Bocchinfuso, Gianfranco, Tartaglia, Marco, and Stella, Lorenzo

Abstract

We developed a new class of inhibitors of protein-protein interactions of the SHP2 phosphatase, which is pivotal in cell signaling and represents a central target in the therapy of cancer and rare diseases. Currently available SHP2 inhibitors target the catalytic site or an allosteric pocket but lack specificity or are ineffective for disease-associated SHP2 mutants. Considering that pathogenic lesions cause signaling hyperactivation due to increased levels of SHP2 association with cognate proteins, we developed peptide-based molecules with nanomolar affinity for the N-terminal Src homology domain of SHP2, good selectivity, stability to degradation, and an affinity for pathogenic variants of SHP2 that is 2-20 times higher than for the wild-type protein. The best peptide reverted the effects of a pathogenic variant (D61G) in zebrafish embryos. Our results provide a novel route for SHP2-targeted therapies and a tool for investigating the role of protein-protein interactions in the function of SHP2.

Published
2021

9. Targeting Oncogenic Src Homology 2 Domain-Containing Phosphatase 2 (SHP2) by Inhibiting Its Protein-Protein Interactions

Author

Hubrecht Institute with UMC, Bobone, Sara, Pannone, Luca, Biondi, Barbara, Solman, Maja, Flex, Elisabetta, Canale, Viviana Claudia, Calligari, Paolo, De Faveri, Chiara, Gandini, Tommaso, Quercioli, Andrea, Torini, Giuseppe, Venditti, Martina, Lauri, Antonella, Fasano, Giulia, Hoeksma, Jelmer, Santucci, Valerio, Cattani, Giada, Bocedi, Alessio, Carpentieri, Giovanna, Tirelli, Valentina, Sanchez, Massimo, Peggion, Cristina, Formaggio, Fernando, Den Hertog, Jeroen, Martinelli, Simone, Bocchinfuso, Gianfranco, Tartaglia, Marco, Stella, Lorenzo, Hubrecht Institute with UMC, Bobone, Sara, Pannone, Luca, Biondi, Barbara, Solman, Maja, Flex, Elisabetta, Canale, Viviana Claudia, Calligari, Paolo, De Faveri, Chiara, Gandini, Tommaso, Quercioli, Andrea, Torini, Giuseppe, Venditti, Martina, Lauri, Antonella, Fasano, Giulia, Hoeksma, Jelmer, Santucci, Valerio, Cattani, Giada, Bocedi, Alessio, Carpentieri, Giovanna, Tirelli, Valentina, Sanchez, Massimo, Peggion, Cristina, Formaggio, Fernando, Den Hertog, Jeroen, Martinelli, Simone, Bocchinfuso, Gianfranco, Tartaglia, Marco, and Stella, Lorenzo

Published
2021

10. Targeting Oncogenic Src Homology 2 Domain-Containing Phosphatase 2 (SHP2) by Inhibiting its Protein-Protein Interactions

Author

Bobone, Sara, primary, Pannone, Luca, additional, Biondi, Barbara, additional, Solman, Maja, additional, Flex, Elisabetta, additional, Canale, Viviana, additional, Calligari, Paolo, additional, Faveri, Chiara De, additional, Gandini, Tommaso, additional, Quercioli, Andrea, additional, Torini, Giuseppe, additional, Venditti, Martina, additional, Lauri, Antonella, additional, Fasano, Giulia, additional, Hoeksma, Jelmer, additional, Santucci, Valerio, additional, Cattani, Giada, additional, Bocedi, Alessio, additional, Carpentieri, Giovanna, additional, Tirelli, Valentina, additional, Sanchez, Massimo, additional, Peggion, Cristina, additional, Formaggio, Fernando, additional, Hertog, Jeroen den, additional, Martinelli, Simone, additional, Bocchinfuso, Gianfranco, additional, Tartaglia, Marco, additional, and Stella, Lorenzo, additional

Published
2020
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