We are pleased to announce that a paper entitled “Naphthyridine carbamate dimer ligand induces formation of Z-RNA-like fold of disease-related RNA and exhibits a molecular glue characteristics in crystal lattice formation” coauthored by Martyna Mateja-Pluta, Leszek Błaszczyk, Magdalena Bejger, Kazuhiko Nakatani and Agnieszka Kiliszek has been published in Nucleic Acids Research.

This work is a continuation of the research by Kiliszek’s group, focusing on the structural characterization of RNA-driven disorders interacting with small synthetic molecules. It describes the crystallographic structure of the complex of Naphthyridine Carbamate Dimer ligand (NCD) and RNA containing the UGGAA motif associated with Spinocerebellar Ataxia Type 31 (SCA31), as well as the structure of unliganded RNA.

Detailed structural analysis of NCD-RNA interactions revealed that NCD ligand forms direct, non-canonical interactions with RNA. A comparison of RNA in free and bound forms revealed that NCD binding induces large and global structural changes in RNA by switching from the A-RNA to the Z-RNA-like fold. This observation is rare and provides invaluable information on RNA structural properties and RNA-ligand interactions. Additionally, NCD serves as a molecular glue and can be considered for crystal lattice formation and improving the quality of crystals.

Our understanding of the structural nature of RNA-ligand interactions is limited, and the number of RNA-ligand structures is still underrepresented compared to that of proteins. The experimentally determined structures of RNA-ligand complexes support the selection of compounds from libraries for high-throughput screening, optimization of small molecules, and improvement of bioinformatics structural predictions, which remain challenging.

Link to the full paper: https://academic.oup.com/nar/article/53/17/gkaf924/8256624