Synergistic binding of actinomycin D and echinomycin to DNA mismatch sites and their combined anti-tumour effects.

ABSTRACT: Combination cancer chemotherapy is one of the most useful treatment methods to achieve a synergistic effect and reduce the toxicity of dosing with a single drug. Here, we use a combination of two well-established anticancer DNA intercalators, actinomycin D (ActD) and echinomycin (Echi), to screen their binding capabilities with DNA duplexes containing different mismatches embedded within Watson-Crick base-pairs. We have found that combining ActD and Echi preferentially stabilised thymine-related T:T mismatches. The enhanced stability of the DNA duplex-drug complexes is mainly due to the cooperative binding of the two drugs to the mismatch duplex, with many stacking interactions between the two different drug molecules. Since the repair of thymine-related mismatches is less efficient in mis

SUBMITTER: Satange R 

PROVIDER: S-EPMC10164580 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature