Strong and Specific Recognition of CAG/CTG Repeat DNA (5'‐dWGCWGCW‐3') by a Cyclic Pyrrole‐Imidazole Polyamide

Y Hirose, T Ohno, S Asamitsu, K Hashiya… - …, 2022 - Wiley Online Library
Y Hirose, T Ohno, S Asamitsu, K Hashiya, T Bando, H Sugiyama
ChemBioChem, 2022Wiley Online Library
Abnormally expanded CAG/CTG repeat DNA sequences lead to a variety of neurological
diseases, such as Huntington's disease. Here, we synthesized a cyclic pyrrole‐imidazole
polyamide (cPIP), which can bind to the minor groove of the CAG/CTG DNA sequence. The
double‐stranded DNA melting temperature (Tm) and surface plasmon resonance assays
revealed the high binding affinity of the cPIP. In addition, next‐generation sequencing
showed that the cPIP had high specificity for its target DNA sequence.
Abstract
Abnormally expanded CAG/CTG repeat DNA sequences lead to a variety of neurological diseases, such as Huntington's disease. Here, we synthesized a cyclic pyrrole‐imidazole polyamide (cPIP), which can bind to the minor groove of the CAG/CTG DNA sequence. The double‐stranded DNA melting temperature (Tm) and surface plasmon resonance assays revealed the high binding affinity of the cPIP. In addition, next‐generation sequencing showed that the cPIP had high specificity for its target DNA sequence.
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