1,3-Di(quinolin-2-yl)guanidine binds to GGCCCC hexanucleotide repeat DNA in C9ORF72.
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Shibata T, Murakami E, Nakatani K
1,3-Di(quinolin-2-yl)guanidine binds to GGCCCC hexanucleotide repeat DNA in C9ORF72.
Bioorg Med Chem Lett. 2018 Aug 1;28(14):2364-2368. doi: 10.1016/j.bmcl.2018.06.032. Epub 2018 Jun 18.
- PubMed ID
- 29929880 [ View in PubMed]
- Abstract
Aberrant expansion of GGGGCC (G4C2) hexanucleotide repeat (HNR) in the first intron of C9ORF72 has been found in frontotemporal dementia and amyotrophic lateral sclerosis (FTD/ALD). The non-canonical DNA structures of the expanded repeats are causative to repeat instability leading to contraction and expansion. We demonstrate that 1,3-di(quinolin-2-yl)guanidine (DQG) binds to GGCCCC/GGCCCC (G2C4/G2C4) motif in double stranded DNA and also antisense G2C4 HNR DNA in C9ORF72. Large increase in the melting temperature of dsDNA containing the G2C4/G2C4 motif was confirmed by the binding of DQG. The marked CD spectral changes indicated structural transition of d(G2C4)9 from i-motifs and/or hairpins to DQG-stabilized d(G2C4)9 structures.