U Know Flashcards
What are the components of a DNA nucleotide
Deoxyribose sugar
Phosphate group
Nitrogenous base (Adenine (A), Thymine (T), Cytosine(C), Guanine (G)
What is the difference between a nucleoside and nucleotide
A nucleoside consists of a nitrogenous base attached to a deoxyribose sugar
A nucleotide is formed when a phosphate group is added to the nucleoside bond
How are the DNA strands oriented in the double helix
The 2 strands are antiparallel. One runs in 5’ to 3’ direction + the other in the 3’ to 5’ direction
How do DNA bases pair, and how many hydrogen bonds are involved
Adenine pairs with Thymine via 2 hydrogen bonds
Guanine pairs with Cytosine via 3 hydrogen bonds
What stabilises the DNA double helix
Hydrogen bonds between base pairs + base-stacking interactions (hydrophobic forces between adjacent bases)
What are the major + minor grooves in DNA, and why are they important
Major + minor grooves are spaces formed by the helical structure - providing binding sites for proteins + drugs to interact with DNA
Why are DNA bases considered nucleophillic
They have nitrogenous + oxygen atoms with lone pairs of electrons, making them capable of donating electrons to electrophiles
Which DNA site is targeted by alkylating agents
The N7-G>N1-A>N3-C, N3-T
What are electrostatic interactions in DNA-alkylating reactions
The attraction between negatively charged nucleophilic DNA sites + positively charged or electron-deficient electrophilic agents
What are the HOMO + LUMO in the context of DNA interactions
HOMO of a nucleophile donates electrons while LUMO of an electrophile accepts electrons, facilitating bond formation
How do nitrogen mustards alkylate DNA
They form a reactive aziridinium ion, which binds to nucleophilic sites on DNA, primarily the N7-G, causing cross-links + disrupting DNA function
What is the anchimeric assistance in the formation of the aziridinium ion
It is the stabilisation of the intermediate state by the lone pair of electrons on the nitrogen atom, making the formation of the aziridinium ion energetically favourable
What type of cross-links do bifunctional alkylating agents create in DNA?
Intrastrand (within the same strand) + interstrand (between 2 strands) cross-links, which prevent DNA strand separation
How does DNA respond to alkylating damage
DNA fragmentation can occur through hydrolytic reactions or during attempts by cellular repair enzymes to remove alkylated bases
How are alkylating agents used in cancer therapy
They damage DNA in rapidly dividing cancer cells, inhibiting replication + causing apoptosis.
Why is understanding DNA structure important for developing cancer therapies?
The double helix’s grooves + nucleophilic sites provide specific targets for drugs, allowing the design of agents that can disrupt critical DNA functions in cancer cells
Grooves in DNA
Major + minor grooves are lined with hydrogen bond donors and acceptors, providing sites for protein + drug binding. They are crucial for DNA-protein interactions + are targets for Chemotherapeutic agents
Nucleoside definition
A nitrogenous base
Purine: Adenine, Guanine
Pyrimidine: Cytosine, Thymine
Attached to a deoxyribose sugar
Nucleotide definition
One or more phosphate groups attach to a nucleoside. Nucleotides linked by phosphodiester bonds
Preferred sites for alkylation
Accessibility to nucleophilic sites can be influenced by their position within the DNA double helix’s. Sites in the major + minor grooves are more exposed - and thus more susceptible to attack
The interaction between the nitrogen/oxygen atoms with an alkylating agent
When a nucleophile interacts with an electrophile the HOMO of the nucleophile overlaps with the LUMO of the electrophile. This overlap allows the electrons from the HUMO of the nucleophile to flow into the LUMO of the electrophile resulting in the formation of a covalent bond
