A small molecule binding to TGGAA pentanucleotide repeats that cause spinocerebellar ataxia type 31

Bioorg Med Chem Lett. 2023 Jan 1:79:129082. doi: 10.1016/j.bmcl.2022.129082. Epub 2022 Nov 19.

Abstract

Spinocerebellar ataxia type 31 is an autosomal dominant neurodegenerative disease caused by aberrant insertion of d(TGGAA)n into the intron shared by brain expressed, associated with Nedd4 and thymidine kinase 2 genes in chromosome 16. We reported that a naphthyridine dimer derivative with amidated linker structure (ND-amide) bound to GGA/GGA motifs in hairpin structures of d(TGGAA)n. The binding of naphthyridine dimer derivatives to the GGA/GGA motif was sensitive to the linker structures. The amidation of the linker in naphthyridine dimer improved the binding property to the GGA/GGA motif as compared with non-amidated naphthyridine dimer.

Keywords: DNA-binding small molecule; Mismatched base pair; Spinocerebellar ataxia type 31; TGGAA pentanucleotide repeats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry
  • Amides / pharmacology
  • Humans
  • Microsatellite Repeats* / drug effects
  • Naphthyridines* / chemistry
  • Naphthyridines* / pharmacology
  • Polymers
  • Spinocerebellar Ataxias / genetics
  • Spinocerebellar Ataxias / metabolism

Substances

  • Amides
  • Naphthyridines
  • Polymers

Supplementary concepts

  • Spinocerebellar Ataxia 31