Nucleic acids as Drug Targets Ch 6 & 9

Question 1

Primary structure of nucleic acids

Answer 1

Nucleotides bound bind via sugar-phosphate backbone

Question 2

Nucleotide vs. Nucleoside

Answer 2

Nucleotide: Phosphate+sugar+base
Nucleoside: Sugar+base

Question 3

Purines vs. Pyrimidines

Answer 3

Purine: Adenine, Guanine (2 ring)
Pyrimidine: Cytosine, Thymine (1 ring)

Question 4

Secondary structure of DNA

Answer 4

Double helix with ionized sugar phosphate backbone facing outward interacting with water and bases point inward, paired, and stacked

Question 5

Base pairing

Answer 5

Adenine-Thymine (2 H-bonds)

Cytosine-Guanine (3 H-bonds)

Question 6

Tertiary Structure of DNA

Answer 6

Supercoiling: helix coils into 3D shape

Question 7

Quinolone, Fluoroquinolone

Answer 7

Antibacterial agents which acts as inhibitors of enzyme that relieves strain when DNA is unraveled for replication.

Question 8

RNA vs DNA primary structure (2)

Answer 8

Ribose instead of deoxyribose

Uracil instead of thymine

Question 9

Secondary structure of RNA

Answer 9

Single stranded with some areas of helical secondary structure on same strand (tRNA)

Question 10

Three types of RNA involved in protein synthesis

Answer 10

mRNA: relays code for protein from DNA
tRNA: adapter linking triplet code on mRNA to specific amino acid
rRNA: important is structure and catalytic activity of ribosomes

Question 11

Transcription

Answer 11

Copying of segment of DNA which codes for a specific protein to RNA

Question 12

Translation

Answer 12

Protein synthesis: tRNA with new amino acid enters on A site and peptide bond is formed. Ribosome shifts so that tRNA with chain is in P site and uncharged tRNA is ejected.

Question 13

Structure of tRNA

Answer 13

Nontraditional bases, amino acid bound to 3’ end, anticodon that is complementary to triplet code (codon) on mRNA

Question 14

Intercalating agents (2 examples)

Answer 14

Contain planar aromatic or heteroaromatic ring system thaht slip between the layers of nucleic acid pairs and disrupt the shape of helix. Prevents replication and transcription. inhibits topoisomerase II. (Proflavine, dactinomycin, doxorubicin, quinine, chloroquine)

Question 15

Topoisomerase II

Answer 15

Relieves strain in DNA helix by temporarily cleaving DNA via a covalent bond between DNA and a tyrosine residue and crossing an intact strand through

Question 16

Proflavine

Answer 16

Planar tricyclic intercalating agent used as topical antibacterial agent

Question 17

Anitimalarial intercalating agents

Answer 17

Quinine, chloroquine

Question 18

Alkylating agents (3 ex)

Answer 18

Highly electrohilic groups form a covalent bond to nucleophilic groups in DNA, preventing replication and transcription. (Ex. mechlorethamine, mitomycin C, cisplatine).

Question 19

Mechanism of alkylating agent

Answer 19

N-7 of guanine attacks aziridine ring. This can occur twice to cause cross-linkages.

Question 20

Mechanism of mitomycin C

Answer 20

Reduced and methoxy group removed by body. DNA base adds by Michael addition and another DNA base attacks carboxamide resulting in decarboxylation.

Question 21

Chain cutters (2 ex)

Answer 21

Abstracts H from DNA to generate radicals which react with oxygen. (ex. bleomycin, calicheamicin)

Question 22

5 Examples Antibiotics that act on rRNA

Answer 22

Chloramphenicol, chlortetracycline, rifamycins, streptomycin, erythromycin

Question 23

Antisense Therapy

Answer 23

Uses a small (20 bases) complementary RNA molecule to prevent protien synthesis

Question 24

Advantages of antisense therapy (4)

Answer 24

Has same effect as enzyme inhibitor or receptor antagonist, highly specific, small dose, and less side effects.

Question 25

Disadvantages of antisense therapy (2)

Answer 25

Only exposed section of mRNA must be targeted, poor pharmacokinetics due to instability (short lifetime) and polarity (poor absorption) of oligonucleotides,

Question 26

Antiviral agents related to nucleic acid building blocks (3)

Answer 26

Azidothymidine (AZT), Acyclovir, Famciclovir has chain terminating groups.