Nucleic acids Flashcards
What are the 5 different types of agents for targeting DNA?
intercalating agents Non intercalating agents -topoisomerase poisons Alkylating agents Chain cutters Chain terminators
How do intercalating agents work?
Planar or heteroaromatic structures insert between DNA base pairs e.g major or minor groove - form a stacking interaction held in place by VDW - so we stabilise the DNA
How do non-intercalating agents work?
Interact with the DNA-enzyme complex to inhibit biological function - bind only after DNA has been cleaved by topoisomerase- the planar core of the drug binds to DNA and stacks through VDW and substituents at C6 and C7 can bind to enzyme - the Oxygen from C-O forms hydrogen bonds with DNA - prevents supercoiling
How do alkylating agents work?
Highly electrophilic molecule binds to nucleophilic groups on the DNA bases - forms cross links to stop the enzyme reading through the cross links
inter strand where hinder separation of strands so no transcription or replication
Intrastrand changes in DNA structure to mask it from the enzymes and thus no trans/replication
How do chain cutters work
Cleave DNA and then prevent DNA ligase enzyme from repairing the damage- this is via a radical mechanism resulting in oxidative cleavage of DNA - radicals make breaks in the DNA
How do chain terminators work?
Inhibit DNA replication by acting as false substrates - they lack the functional groups needed for further chain growth so when they get incorporated into the growing DNA chain, the replication gets terminated e.g acyclovir which has incomplete sugar
Why would targeting nucleic acids in drug therapy lead to therapeutic outcomes?
If a drug can inhibit transcription then it can prevent ell division and thus growth e.g cancer cels e.g alkylating agent which can form crosslinks between DNA bases to stop the enzymes reading between the crosslinks - thus no transcription.
Binding of a molecule to a specific DNA sequence could turn off expression of a protein which could lead to downstream changes in protein expression and cell function
What is a disadvantage to using alkylating agents as drug therapy?
They can react with other nucleophilic groups in the body so lack sensitivity and thus can produce toxic side effects
