Intercalation and New Targets Flashcards
How is DNA topoisomerase II targeted in cancer chemotherapy?
The drugs which target topoisomerase II kill cells by trapping the covalent complex. TOP2 mediated DNA damage is repaired by multiple pathways and requires double strand break repair pathways and other protein adduct removal pathways.
What are the side effects of TOP2 targeting?
Formation of secondary malignancies arising from drug translocations.
How are transcription drugs targeted by DNA intercalating drugs?
Doxorubicin and SN-38 interacts and stabilises the TOP2 DNA complexes to produce a cleavable complex which results in DNA strand breakage associated with protein DNA complex.
Pluramycin binds peripherally to the TATA binding protein box complex. Alkylation by pluramycin is enhanced by TBP binding to the TATA box as a result TBP is immobilised on the DNA.
What is telomerase?
An enzyme which adds TTAGGG to the 3’ end of DNA strands in the telomerase regions, which are found at the ends of eukaryotic chromosomes. The region of repeated nucleotide called telomerases contains non-coding DNA material and prevents constant loss of important DNA from chromosomes ends.
What is the equilibrium between the double stranded DNA structures and the G-quadruplexes dependent on?
They are dependent on helicases that unwind the quadruplex and chaperone proteins that are required for its formation.
G-quadruplex interactive drugs can either inhibit helicases or facilitate formation of new quadruplexes or can sequester newly formed G-quadruplexes.
