DNA drugs 1- mech Flashcards
where do classical anti-tumor agents work?
on target DNA replication
what agents act directly on target DNA?
- alkylating agents
- cisplantin
- natural products such as bleomycin
what agents act indirectly on target DNA?
- DNA processing enzymes (topoisomerase
- DNA synthesis
what are intercalating agents and how do work?
they are agents that have a planar aromatic heteroaromatic ring system that can slip between the layers of nucleic acid pairs and disrupt the shape f the helix
what do they do intercalating agents overall?
- they prevent replication and transcription
- can inhibit topoisomerase
what is proflavine?
used to target bacterial DNA its a topical antibacterial agent used in second world war its too toxic for systemic use
what kind of changes need to occur for the intercalator to fit inbetween base pairs?
DNA must open a space between its base pairs by unwinding so bases seperate
what functional group does proflavine have that helps it work?
its amino substituents as they are protonated and charged so they point outwards and ionically bond to the oxygen on the phosphate of the DNA
what is dactinmycin and how does it work?
- it intercalates via minor groove of DNA
- it prevents unwinding of DNA
- blocks transcription by blocking DNA-dependant RNA polymerase
- it has extra binding to sugar phosphate backbone by cyclic peptide
what is doxorubicin (adriamycin) and how does it work?
- intercalates via major groove of DNA
- blocks the action of topoisomerase II by stablislising the DNA enzyme complex
- thers also extra binding to sugar phosphate by NH3
what is the most known application for intercalators?
gel electrophoresis
whats the main development needed for intercalators?
testing its toxicity
what do minor groove binding agents do overall?
can inhibit topoisomerase enzymes and prevent protein binding
what are minor groove binding and how does it work?
- they are curved aromatic compounds that match that of the floor if the minor groove
- they are hydrogen bond donors on the inside edge
what do control gene transcription agents do?
they target minor grooves and recognise molecules and bind to specific sequences
