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.

ABSTRACT: The naphthyridine carbamate dimer (NCD) is a small molecule that recognizes disease-related RNA containing UGGAA repeats associated with spinocerebellar ataxia type 31 (SCA 31) and alleviates the disease phenotype in vitro and in vivo. In this study, we use X-ray crystallography to elucidate the mode of NCD binding in detail. We determine the crystal structures of the RNA-NCD complex and a structure of unliganded RNA. The NCD interacts differently than in previously reported nuclear magnetic resonance structure, forming pseudo-canonical base pairs with guanosine residues located on the same RNA strand. Furthermore, in one of the complexes, the ligand is located between symmetry-related RNA molecules, exhibiting a molecular glue characteristics in crystal lattice formation. The comparison o

SUBMITTER: Mateja-Pluta M 

PROVIDER: S-EPMC12448875 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature