Topoisomerases Flashcards
T/F: Anti-cancer topoisomerase drugs work by converting the enzyme into a target that damage DNA rather than by simply inhibiting enzyme activity
True
What are the major classes of topoisomerases targeting agents
Camptothecins, Epidophyllotoxins, anthracyclines
What are catenanes, what must happen for seperation
double stranded DNA linked, cutting
What are the enzymes that transiently cut DNA, how
Topoisomerases, tyrosine apart of topoisomerases attacks the phosphodiester backbone of DNA forming a covalent bond and “cutting” the DNA
Which topoisomerases cut single strand DNA, which cut DS DNA
Toposisomerases 1, topoisomerases 2
What are the topoisomerases targeted in drug therapy
Topoisomerase 1B
What are the two types of topoisomerases and what are they used for
Top-2 alpha: replication and cell division, Top-2 beta: transcription
What anticancer class target topoisomerase 1, caveat
Campothothecins, not approved by FDA (failed due to unpredictable toxicities)
What are three known topoisomerase 2 anti-cancer drugs
Etoposide, doxorubicin, and mAMSA
What is interacalation
The drug binds to DNA through pi-pi interactions with DNA bases due to a planar structure
What common top-2 anticancer drug does not intercalate despite its planar structure
Etoposide
T/F: Top-1 is not essential for life but Top-2 is
True
What is the MOA of campotheticans
Top-1 cleaves DNA then Campotheticins slide into to intercalate with DNA causing Top-1 to no longer be able to seal the break
T/F: Topoisomerase poisons are irreversible
False: If the drugs are washed away damages made can be fixed
What is the enzyme that is known for fixing topoisomerase damage, MOA
Tyrosyl DNA phophodeisterase (TDP1), offers histidine for a replacement for tyrosine
