BOPC1 Enantiomers Preparation and HuR Interaction Study. From Molecular Modeling to a Curious DEEP-STD NMR Application.

Autor:	Volpe SD; Department of Drug Sciences, Medicinal Chemistry and Technology Section, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy.; Department of Chemistry, University of Milan, Via Golgi 19, 20133 Milano, Italy., Listro R; Department of Drug Sciences, Medicinal Chemistry and Technology Section, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy., Parafioriti M; Department of Drug Sciences, Medicinal Chemistry and Technology Section, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy., Di Giacomo M; Department of Drug Sciences, Medicinal Chemistry and Technology Section, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy., Rossi D; Department of Drug Sciences, Medicinal Chemistry and Technology Section, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy., Ambrosio FA; Department of Health Sciences, University 'Magna Græcia' of Catanzaro, Viale Europa, 88100 Catanzaro, Italy., Costa G; Department of Health Sciences, University 'Magna Græcia' of Catanzaro, Viale Europa, 88100 Catanzaro, Italy.; Net4Science Academic Spin-Off, University 'Magna Græcia' of Catanzaro, Campus 'S. Venuta', Viale Europa, Germaneto, 88100 Catanzaro, Italy., Alcaro S; Department of Health Sciences, University 'Magna Græcia' of Catanzaro, Viale Europa, 88100 Catanzaro, Italy.; Net4Science Academic Spin-Off, University 'Magna Græcia' of Catanzaro, Campus 'S. Venuta', Viale Europa, Germaneto, 88100 Catanzaro, Italy., Ortuso F; Department of Health Sciences, University 'Magna Græcia' of Catanzaro, Viale Europa, 88100 Catanzaro, Italy.; Net4Science Academic Spin-Off, University 'Magna Græcia' of Catanzaro, Campus 'S. Venuta', Viale Europa, Germaneto, 88100 Catanzaro, Italy., Hirsch AKH; Helmholtz Institute for Pharmaceutical Research Saarland (HIPS)-Helmholtz Centre for Infection Research (HZI), Department of Drug Design and Optimization, Campus Building E8.1, 66123 Saarbrücken, Germany.; Department of Pharmacy, Saarland University, Campus Building E8.1, 66123 Saarbrücken, Germany., Vasile F; Department of Chemistry, University of Milan, Via Golgi 19, 20133 Milano, Italy., Collina S; Department of Drug Sciences, Medicinal Chemistry and Technology Section, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy.
Jazyk:	angličtina
Zdroj:	ACS medicinal chemistry letters [ACS Med Chem Lett] 2020 Jan 28; Vol. 11 (5), pp. 883-888. Date of Electronic Publication: 2020 Jan 28 (Print Publication: 2020).
DOI:	10.1021/acsmedchemlett.9b00659
Abstrakt:	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. Competing Interests: The authors declare no competing financial interest. (Copyright © 2020 American Chemical Society.)
Databáze:	MEDLINE
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