Nucleic Acids

Question 1

What are nucleic acids composed off

Answer 1

4 or heterocyclic bases

Question 2

what are the 2 pyrimidne bases

Answer 2

cytosine thymine

Question 3

what are the 2 purine bases

Answer 3

adenine guanine

Question 4

what do heterocylic base attach to form a nucleoside

Answer 4

5 memebered sugar unit

Question 5

at what positions do phosphate linkages form

Answer 5

3’ and 5’

Question 6

what is the uncommon base

Answer 6

uracil and it is a replacement for thymine

Question 7

describe an A - Dna helix

Answer 7

RNA RNA and RNA DNA Helix with a short wide shape

deep narrow major grove with a wide shallow minor groove

base pair tilted to helix axis

c3’ endo

Question 8

describe a B - DNA helix

Answer 8

DNA DNA with a narrow longer helix

Wide major groove

Narrow minor groove

base pair perpedicular to helix axis

c2’ endo

Question 9

describe a Z - DNA helix

Answer 9

left handed

narrow long helix

narrow deep minor group

alternating anti syn conformation

Question 10

what are the different ways a drug molecule can interact

Answer 10

intercalating agents

topoisomerism poisons

alkylating agents

chain cutters

chain terminators

Question 11

describe how a DNA forms a protein

Answer 11

DNA replicates
Transcription
RNA
Translation
Protein

Question 12

what are intercalating agnets

Answer 12

contain planar or heteroaromatic structures which fit between the DNA base pairs

Question 13

what are intercalating agents held in place by

Answer 13

van der waals interactions

Question 14

what is doxorubicin

Answer 14

highly effective anti cancer drug

Question 15

what does doxorubicin do

Answer 15

intercalates with DNA

Question 16

how does doxuribicin intercalate with DNA

Answer 16

approaches from the minor groove and intercalates using the planar tricyclic structure

Question 17

what does doxorubicin do

Answer 17

hinders the normal action of topoisomerase II, an enzyme involved in replication.

Question 18

what is doxorubicin referred to

Answer 18

inhibit the enzyme so is referred to as a poison

Question 19

what is super coiling

Answer 19

dna must be coiled int oa more compact structure to fit into the nucleus

Question 20

what does super coiling require

Answer 20

super coiling requries one stretch of DNA to cross over another and this process is catalysed by topoisomerase enzymes

Question 21

what is doxorubicins effect on super coiling

Answer 21

stablises the enzyme DNA complex and hinders the process

Question 22

what do non intercolating poisons do

Answer 22

fluroquinolones can interact with the DNA enzyme complex and inhibit biological function

The binding site for the drug appears only after DNA has been cleaved by the topoisomerase enzyme.

Planar core will stack through Van der Waals interactions, substituents at C6 and C7 positions can bind to the enzyme.

Carbonyl oxygen can form H-bonds with DNA.

Question 23

what is an alkylating agent

Answer 23

highly electrophilic molecule which will react with necleophilic groups within the heterocyclic DNA bases

Question 24

what can alkylating agents form

Answer 24

inter or intra strand crosslink

Question 25

what do interstand crosslinks do

Answer 25

disrupt replication and transcription by hindering separation of strands

Question 26

what do intrastrand crosslinks do

Answer 26

mask DNA structure from enzymes involved in replication and transcription

Question 27

what are the downside of alkylating agents

Answer 27

lack selectivity

Question 28

how do alkylating agents act as anti cancer

Answer 28

they reduce toxicity by formation of the active species during metabolism

Question 29

what is one of the most widely used anticancer drugs in medicine

Answer 29

cis platin

Question 30

what happens when cis platin enters the cellular environment

Answer 30

chlroide substituents are dispalaced by water active species then forms intrastrand crosslinks in regions contraining adjacent guanine bases attachement of the drug is thought to disturb the hydrogen bonding between the heterocyclic bases resulting in local unwinding of the helix very lowselectivity for cancer cells causes high toxicity of drug

Question 31

what are chain cutters

Answer 31

these drugs will cleave DNA and prevent the enzyme DNA ligase from repairing the damage thought to work through a radical mechanism resulting in oxidative cleavage of the DNA structure

Question 32

what do chain terminators do

Answer 32

inhibit DNA replication by acting as false substrate

Question 33

what do chain terminateors lack

Answer 33

functional groups requriered for further chain growth so incorporation into a growing DNA chain will reuslt in termination

Question 34

what are chain terminators used for

Answer 34

antiviral drugs treatment of HIV targeting reverse transcriptase

Question 35

what does stabilisation of the gene helix

Answer 35

stabilisation of the double helix will inhibit the processes involved in transcription and ultimately protein synthesis

Question 36

what are the two modes of action of antisense therapy

Answer 36

steric block cleavage by RNaaseH

Question 37

what are the optimal characteristics of RNA

Answer 37

``` duplex stability specificity nuclease stability cellular uptake toxicity ```

Question 38

what does a too short chain mean

Answer 38

lead to targetting of other regions of RNA

Question 39

what does a too long chain mean

Answer 39

mismatched sequences

Question 40

what is the ideal chain length

Answer 40

20-25 bases

Question 41

what shows the greatest therapeutic potential

Answer 41

requires continueous stretch of DNA bases of 6-10 residues

Question 42

what does modification require

Answer 42

requires continuous stretch of DNA bases of 6-10 residues containing a phosphodiester or phosphothioate linkage

Question 43

what form of linkage are more resistant to nuclease degradation

Answer 43

phosphothiaote linkage

Question 44

what do 2nd generation antisense drugs use

Answer 44

a gapmer principle

Question 45

2nd generation antisense

Answer 45

Core region of phosphorothioate linkages are flanked by regions containing other modification. They enhance the stability of DNA:RNA duplex, and therefore modifications that induce the C3’-endo sugar pucker are desired. Also enhancement of nuclease stability is a consideration. These modifications can also be used for the steric block approach.

Question 46

what can small RNA molecules present in the cell be used to control

Answer 46

gene expression and protect against viruses

Question 47

what are micro RNA

Answer 47

small double stranded RNA molecules are produced from larger RNA sequences by the dicer enzyme

Question 48

what are micro RNA produced from

Answer 48

larger RNA sequences by the dicer enzyme

Question 49

describe RNA INTERFERANCE

Answer 49

The miRNA then binds to a complex of enzymes known as RISC (RNA inducing silencing complex). In the RISC complex one strand is discarded to produce the small interfering RNA sequence (siRNA). This binds to a complementary mRNA and induces cleavage of the mRNA.

Question 50

Key points of RNA interference

Answer 50

dsRNA cleaved by Dicer to give miRNA. Loading into RISC complex gives siRNA. Recognition of mRNA by active RISC complex. Cleavage of mRNA results in inhibition of protein synthesis. Cleavage of viral RNA halts attack.

Question 51

what do siRNA do

Answer 51

silence target gene

Question 52

what is antigene therapy

Answer 52

similar to antisense approach but targets the DNa double helix rather than the RNA Conventional drugs that target DNA have low selectivity for the target sequence targeting of the DNA base pair will provide increased specificity