4.4 Article

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

Journal

CHEMBIOCHEM
Volume 23, Issue 2, Pages -

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.202100533

Keywords

CAG; CTG repeats; DNA recognition; pyrrole-imidazole polyamides; triplet repeats

Funding

  1. AMED [JP21am0101101]
  2. JSPS KAKENHI [JP16H06356, 21H04705, 20H05936]
  3. NIH [RO1CA236350, 21J22276]
  4. Grants-in-Aid for Scientific Research [21H04705, 20H05936] Funding Source: KAKEN

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A cyclic pyrrole-imidazole polyamide (cPIP) was synthesized to bind to the abnormal expanded CAG/CTG repeat DNA sequences, showing high binding affinity and specificity for its target DNA sequence.
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 (T-m) 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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