Nucleic Acids

Question 1

Pyrimidine numbering

Answer 1

• Assign priority to nitrogen adacent to C=C bond
• Look for other nitrogen in ring(direction of numbering)

Question 2

Purine numbering

Answer 2

• Assign priority to the nitrogen in the larger ring, farthest away from the ring junction.
• Look for the second nitrogen in the larger ring, this is the direction that you will number.
• Number the rest of the entire larger ring.
• Move onto the smaller ring, and number the double bonded nitrogen.
• Number the rest of the atoms in the smaller ring (clockwise).

Question 3

Why does DNA contain thymine

Answer 3

• Cytosine can spontaneously convert to uracil through hydrolytic deamination
• DNA repair enzymes recognize these mutations and replaces mutant Us with Cs
• Nature solves this by using thymine(5-methyl U) in place of uracil

Question 4

Naturally occurring derivatives

Answer 4

• Hypoxanthine: Deamination of adenine
• Xanthine: Deamination of guanine
• 4-thiouridine: replacement of uracil carbonyl with thiol(S) group
• Inosine: hypoxanthine attached to ribose sugar
• Ribothymidine: Thymine attached to ribose sugar
• Psuedouridine: connects ribose sugar via C1 - C5 linkage
• Dihydrouridine: Made from hydrogenation of double bond in uracil

Question 5

Steudel: Phosphate based polymer

Answer 5

• Linking occurs between phosphate groups
• Base bound to sugar hangs off phosphate

Question 6

Levene/Jacobs: Carbohydrate based polymer

Answer 6

• Riboses linked directly together
• Phosphates and nitrogenous bases hang off carbohydrate backbone

Question 7

Takahashi: Tetranucleotide(cyclic) hypothesis

Answer 7

• Cyclic tetramer
• Correctly depicted base-sugar-phosphate connectivity
• Incorrectly suggest DNA is comprised of independent tetranucleotide units

Question 8

Penny Stacking Model: Astbury/Bell

Answer 8

• DNA was single stranded
• Bases stacked neatly on top of another

Question 9

Base tautomers

Answer 9

• Gullard saw H-bonding occurs between enolic tautomers of nitrogenous base
• Bases primarily exist in keto tautomeric form at physiological pH
• Only keto tautomers form A/T and C/G pairing

Question 10

Pauling: Inside Out Structure

Answer 10

• Correctly identified linear connectivity of DNA and multiple strands
• Incorrectly proposed triple helix

Question 11

Bonding

Answer 11

• Watson-Crick Base Pairing: Standard, most stable base pairing in DNA. Adenine form 2 bond with thymine, while Guanine form 3 bond with cytosine. Purine large ring forms H-bonds.
• Hoogsteen base pairs: Any alternative hydrogen bonding pattern between bases that deviates from Watson-crick
• Wobble base pair: Specific hoogsteen base pair between tRNA and mRNA in translation process. Inosine can bond to either adenine, cytosine, or uracil

Question 12

Melting temperature reflect DNA stability

Answer 12

• Hydrogen bonding, base stacking, and hydrophobic effect can alter melting temperature
• G/C has higher melting temp due to more H-bonds

Question 13

Base-sugar orientation

Answer 13

• In anti, base point away from sugar
• In syn, base directly on top of sugar
• Purines favor anti configuration to avoid steric clashing
• Pyrimidine only found in anti

Question 14

Sugar pucker

Answer 14

• In C2’ endo, 2’ carbon projected above plane of sugar, allow large inter-phosphate distance between nucleotides and more stable. Mostly found in DNA
• In C3’ endo, 3’ carbon projected above plane, decreasing inter-phosphate distance between nucleotides. Found in RNA

Question 15

A, B, Z form helices

Answer 15

• A form found in RNA, adopt anti conformation and is in C3’ endo conformation. Relatively shorter and wider. Bind to minor groove
• B form, adopt anti conformation and is in C2’ endo conformation. Found in DNA. Relatively longer and thinner. Bind to major groove
• Z form, adopt anti for cytosine, and syn for guanine. Prefer C2’ endo conformation. Protein unable to bind to Z DNA