U Know

Question 1

What are the components of a DNA nucleotide

Answer 1

Deoxyribose sugar
Phosphate group
Nitrogenous base (Adenine (A), Thymine (T), Cytosine(C), Guanine (G)

Question 2

What is the difference between a nucleoside and nucleotide

Answer 2

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

Question 3

How are the DNA strands oriented in the double helix

Answer 3

The 2 strands are antiparallel. One runs in 5’ to 3’ direction + the other in the 3’ to 5’ direction

Question 4

How do DNA bases pair, and how many hydrogen bonds are involved

Answer 4

Adenine pairs with Thymine via 2 hydrogen bonds
Guanine pairs with Cytosine via 3 hydrogen bonds

Question 5

What stabilises the DNA double helix

Answer 5

Hydrogen bonds between base pairs + base-stacking interactions (hydrophobic forces between adjacent bases)

Question 6

What are the major + minor grooves in DNA, and why are they important

Answer 6

Major + minor grooves are spaces formed by the helical structure - providing binding sites for proteins + drugs to interact with DNA

Question 7

Why are DNA bases considered nucleophillic

Answer 7

They have nitrogenous + oxygen atoms with lone pairs of electrons, making them capable of donating electrons to electrophiles

Question 8

Which DNA site is targeted by alkylating agents

Answer 8

The N7-G>N1-A>N3-C, N3-T

Question 9

What are electrostatic interactions in DNA-alkylating reactions

Answer 9

The attraction between negatively charged nucleophilic DNA sites + positively charged or electron-deficient electrophilic agents

Question 10

What are the HOMO + LUMO in the context of DNA interactions

Answer 10

HOMO of a nucleophile donates electrons while LUMO of an electrophile accepts electrons, facilitating bond formation

Question 11

How do nitrogen mustards alkylate DNA

Answer 11

They form a reactive aziridinium ion, which binds to nucleophilic sites on DNA, primarily the N7-G, causing cross-links + disrupting DNA function

Question 12

What is the anchimeric assistance in the formation of the aziridinium ion

Answer 12

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

Question 13

What type of cross-links do bifunctional alkylating agents create in DNA?

Answer 13

Intrastrand (within the same strand) + interstrand (between 2 strands) cross-links, which prevent DNA strand separation

Question 14

How does DNA respond to alkylating damage

Answer 14

DNA fragmentation can occur through hydrolytic reactions or during attempts by cellular repair enzymes to remove alkylated bases

Question 15

How are alkylating agents used in cancer therapy

Answer 15

They damage DNA in rapidly dividing cancer cells, inhibiting replication + causing apoptosis.

Question 16

Why is understanding DNA structure important for developing cancer therapies?

Answer 16

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

Question 17

Grooves in DNA

Answer 17

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

Question 18

Nucleoside definition

Answer 18

A nitrogenous base
Purine: Adenine, Guanine
Pyrimidine: Cytosine, Thymine
Attached to a deoxyribose sugar

Question 19

Nucleotide definition

Answer 19

One or more phosphate groups attach to a nucleoside. Nucleotides linked by phosphodiester bonds

Question 20

Preferred sites for alkylation

Answer 20

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

Question 21

The interaction between the nitrogen/oxygen atoms with an alkylating agent

Answer 21

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