Synthesis of 1H-pyrrolo[3,2-h]quinoline-8-amine derivatives that target CTG trinucleotide repeats.
We describe a new molecular design, synthesis, and investigation of small molecules that bind to CTG trinucleotide repeats in DNA. 1H-Pyrrolo[3,2-h]quinoline-8-amine (PQA) has a tricyclic aromatic system with unique non-linear hydrogen-bonding surface complementary to thymine. We have synthesized a series of PQA derivatives with different alkylamino linkers. These PQAs showed binding to pyrimidine bulge DNAs and CNG (N=T and C) repeats depending on the linker structure, while quinoline derivatives lacking the pyrrole ring showed much lower binding affinity. PQA is a useful molecular unit for both CTG and CCG repeat binding.
The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki 567-0047, Japan.
Jun
J
Matsumoto
The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki 567-0047, Japan.
Jinxing
J
Li
The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki 567-0047, Japan.
Chikara
C
Dohno
The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki 567-0047, Japan.
Kazuhiko
K
Nakatani
D000588:Amines / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008024:Ligands; D015394:Molecular Structure; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D018911:Trinucleotide Repeats / Q000187:drug effects*
D000588:Amines; D008024:Ligands; D011758:Pyrroles; D011804:Quinolines; D004247:DNA; C037219:quinoline
CTG repeat; Mismatch base pair; Small molecule ligand