Thermodynamic and spectroscopic investigations of TMPyP4 association with guanine- and cytosine-rich DNA and RNA repeats of C9orf72

Highlights: • The cationic porphyrin (TMPyP4) binds and distorts G-tetrade structures of C9orf72 repeats. • ITC and CD were used to study TMPyP4 interaction with C-rich and G-rich DNA and RNA oligos. • For DNA, the results are consistent with TMPyP4 stacking on the terminal tetrads and intercalation. • For RNA the data are consistent with groove binding and intercalation. • These findings will be helpful in efforts to optimize the binding affinity of TMPyP4 analogs. An expansion of the hexanucleotide repeat (GGGGCC)n·(GGCCCC)n in the C9orf72 promoter has been shown to be the cause of Amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). The C9orf72 repeat can form four-stranded structures; the cationic porphyrin (TMPyP4) binds and distorts these structures.