TMPyP4 porphyrin distorts RNA G-quadruplex structures of the disease-associated r(GGGGCC)n repeat of the C9orf72 gene and blocks interaction of RNA-binding proteins - PubMed (original) (raw)
The porphyrin TMPyP4 binds the C9orf72 RNA G-quadruplex. A, schematic of a G-quartet with 4 guanine residues interacting through Hoogsteen bonding (dashed lines). B, the structure of TMPyP4. C, a parallel-stranded G-quadruplex structure. D, migration of [γ-32P]ATP end-labeled r(GGGGCC)8 in the presence of 10, 25, 50, and 100 μ
m
TMPyP4 in native 8% polyacrylamide gel. E, absorption titration of 15 μ
m
TMPyP4 with (GGGGCC)8 G-quadruplex in the presence of 100 m
m
KCl. Inset, the plot of α (fraction of bound porphyrin versus [RNA] concentration of RNA). All spectra were measured in 10 m
m
Tris-HCl (pH 7.5) and 0.1 m
m
EDTA at room temperature. F, CD titration of 5 μ
m
r(GGGGCC)8 with aliquots of 1
m
TMPyP4 in the presence of 100 m
m
KCl, at 25 °C. G, CD titration of 5 μ
m
r(GGGGCC)5 with aliquots of 1
m
TMPyP4 in the presence of 100 m
m
KCl, at 25 °C. H, CD titration of 5 μ
m
r(GGGGCC)2 with aliquots of 1
m
TMPyP4 in the presence of 100 m
m
KCl, at 25 °C. mdeg, millidegrees; D.E., δ ϵ.