4.4 Review

Application of DNA-Alkylating Pyrrole-Imidazole Polyamides for Cancer Treatment

Journal

CHEMBIOCHEM
Volume 22, Issue 9, Pages 1538-1545

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.202000752

Keywords

cancer; DNA alkylation; DNA recognition; drug discovery; sequence-specificity

Funding

  1. AMED [JP18am0301005, JP18am0101101]
  2. KAKENHI by JSPS [JP16H06356]

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Pyrrole-imidazole (PI) polyamides, which target specific DNA sequences, have shown sequence-specific alkylating activities when conjugated with DNA-alkylating agents, making them potential candidates for developing new anticancer drugs.
Pyrrole-imidazole (PI) polyamides, which target specific DNA sequences, have been studied as a class of DNA minor-groove-binding molecules. To investigate the potential of compounds for cancer treatment, PI polyamides were conjugated with DNA-alkylating agents, such as seco-CBI and chlorambucil. DNA-alkylating PI polyamides have attracted attention because of their sequence-specific alkylating activities, which contribute to reducing the severe side effects of current DNA-damaging drugs. Many of these types of conjugates have been developed as new candidates for anticancer drugs. Herein, we review recent progress into research on DNA-alkylating PI polyamides and their sequence-specific action on targets associated with cancer development.

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