The Hu family of RNA-binding proteins plays a crucial role in post-transcriptional processes; indeed, Hu-RNA complexes are involved in various dysfunctions (i.e., inflammation, neurodegeneration, and cancer) and have been recently proposed as promising therapeutic targets. Intrigued by this concept, our research efforts aim at identifying small molecules able to modulate HuR-RNA interactions, with a focus on subtype HuR, upregulated and dysregulated in several cancers. By applying structure-based design, we had already identified racemic trans-BOPC1 as promising HuR binder. In this Letter, we accomplished the enantio-resolution, the assignment of the absolute configuration, and the recognition study with HuR of enantiomerically pure trans-BOPC1. For the first time, we apply DEEP (differential epitope mapping)-STD NMR to study the interaction of BOPC1 with HuR and compare its enantiomers, gaining information on ligand orientation and amino acids involved in the interaction, and thus increasing focus on the in silico binding site model.
BOPC1 Enantiomers Preparation and HuR Interaction Study : From Molecular Modeling to a Curious DEEP-STD NMR Application / S. Della Volpe, R. Listro, M. Parafioriti, M. Di Giacomo, D. Rossi, F. Alessandra Ambrosio, G. Costa, S. Alcaro, F. Ortuso, A.K.H. Hirsch, F. Vasile, S. Collina. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - 11:5(2020 May 14), pp. 883-888. [10.1021/acsmedchemlett.9b00659]
BOPC1 Enantiomers Preparation and HuR Interaction Study : From Molecular Modeling to a Curious DEEP-STD NMR Application
F. Vasile
;
2020
Abstract
The Hu family of RNA-binding proteins plays a crucial role in post-transcriptional processes; indeed, Hu-RNA complexes are involved in various dysfunctions (i.e., inflammation, neurodegeneration, and cancer) and have been recently proposed as promising therapeutic targets. Intrigued by this concept, our research efforts aim at identifying small molecules able to modulate HuR-RNA interactions, with a focus on subtype HuR, upregulated and dysregulated in several cancers. By applying structure-based design, we had already identified racemic trans-BOPC1 as promising HuR binder. In this Letter, we accomplished the enantio-resolution, the assignment of the absolute configuration, and the recognition study with HuR of enantiomerically pure trans-BOPC1. For the first time, we apply DEEP (differential epitope mapping)-STD NMR to study the interaction of BOPC1 with HuR and compare its enantiomers, gaining information on ligand orientation and amino acids involved in the interaction, and thus increasing focus on the in silico binding site model.File | Dimensione | Formato | |
---|---|---|---|
Manuscript_REVISION_ACS (1).pdf
Open Access dal 02/05/2021
Tipologia:
Post-print, accepted manuscript ecc. (versione accettata dall'editore)
Dimensione
375.27 kB
Formato
Adobe PDF
|
375.27 kB | Adobe PDF | Visualizza/Apri |
acsmedchemlett.9b00659.pdf
accesso riservato
Tipologia:
Publisher's version/PDF
Dimensione
1.53 MB
Formato
Adobe PDF
|
1.53 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.