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

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.

journal_name

ACS Med Chem Lett

journal_title

ACS medicinal chemistry letters

authors

Volpe SD,Listro R,Parafioriti M,Di Giacomo M,Rossi D,Ambrosio FA,Costa G,Alcaro S,Ortuso F,Hirsch AKH,Vasile F,Collina S

doi

10.1021/acsmedchemlett.9b00659

subject

Has Abstract

pub_date

2020-01-28 00:00:00

pages

883-888

issue

5

issn

1948-5875

journal_volume

11

pub_type

杂志文章

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