Nucleic Acid Structure

• How are purines linked to sugars?

  1’-9 (β above)
• How are pyrimidines linked to sugars?

  1’-1 (β above)
• What bases are purines?

  Adenine and Guanine
• What bases are pyrimidines?

  Cytosine, Uracil and Thymine
• Formation of hypoxanthine

  Deamination of adenine at C6
• Formation of Xanthine

  Deamination of Guanine at C2
• Formation of 4-Thiouridine

  Sulfation of Uridine at C4
• Formation of Inosine

  Condensation of Hypoxanthine (sugar attachment)
• Formation of Ribothymidine

  Thymidine connected to ribose instead of deoxyribose
• Formation of Pseudouridine (Ψ)

  Glycosidic linkage of Uridine at C5 instead of N1
• Formation of Dihydrouridine

  Reduction of Uracil
• Who created the Phosphate-based Polymer?

  Steudel
• Phosphate-based Polymer comments

  Polymer linked via P, P missing negative charge, sugar-bases hang off (no H-bonding)
• Who created the Carbohydrate-based Polymer?

  Levene/Jacobs
• Carbohydrate-based Polymer comments

  Some phosphates hanging off, carbohydrates linked together, bases hanging off
• Who created the Tetranucleotide Hypothesis (Cyclic Tetramer)?

  Takahashi
• Tetranucleotide Hypothesis (Cyclic Tetramer) comments

  Correct connectivity between bases + sugar, contains 3’-5’ phosphodiester linkages
• Who created the Tetranucleotide Hypothesis (Linear Tetramer)?

  Levene/Tipson
• Tetranucleotide Hypothesis (Linear Tetramer) comments

  Very linear structure, only had 4 bases
• Who created the (Extended) Single-stranded DNA structure?

  Astbury/Bell
• (Extended) Single-stranded DNA Structure comments

  Planar sugars and bases (problem) – due to use of enolic forms for hydrogen bonding, repeating structures
• Who created the 3-stranded Structure (Inside-Out)?

  Pauling
• 3-stranded Structure (Inside-Out) comments

  Correct identification of linear components, phosphates down the middle not possible due to their significant negative charge
• What was the consequence of using the enolic form of the bases?

  Altered H-bonding pattern with structures
• Keto vs Enol bases

  Keto contains carbonyl, Enol contains hydroxyl
• What did Chargaff’s rules state?


  Ratio of purines to pyrimidines was 1:1 (A:T = 1:1, G:C = 1:1)
• What are the three forces that stabilize DNA structure?

  Hydrogen bonding, dipole interactions, hydrophobic effect
• What are canonical Watson-Crick Base Pairs?

  Basic, normal pairing between bases (A-T, G-C)
• What are Hoogsteen Base Pairs?

  Correct base pairs (A-T, G-C) with altered (different) H-bonding pattern (typically seen in RNA)
• What are Wobble Base Pairs?

  Any pairing between two nucleotides that does not follow Watson-Crick base pair rules
• What are G-quadruplex structures?

  Structures found in telomeres formed by strand rich in guanine via Hoogsteen hydrogen bonding

  
• What indicates DNA stability

  Strand’s melting temperature ($T_m$)
• What factors control DNA/RNA structure?

  Base-sugar orientation, sugar pucker
• What two orientations can a base achieve?

  Syn – above sugar, Anti – away from sugar
• Why can’t pyrimidines be in the syn conformation?

  Leads to increased steric clashing
• For which bases is the syn conformation more unfavourable?

  Pyrimidines
• What are the characteristics of C2’-endo sugar pucker?

  C2’ pointing out, large inter-phosphate distance
• What are the characteristics of C3’-endo sugar pucker?

  C3’ pointing out, small inter-phosphate distance
• What sugar pucker is preferred for DNA?

  C2’-endo
• What sugar pucker is preferred for RNA?

  C3’-endo