Chapter 19 (part 1)
Nucleic Acids
Nucleic Acids Are Essential For
Information Transfer in Cells
• Information encoded in a DNA
molecule is transcribed via synthesis
of an RNA molecule
• The sequence of the RNA molecule
is "read" and is translated into the
sequence of amino acids in a
protein.
Central Dogma of Biology
Nucleic Acids
• First discovered in 1869 by Miescher.
• Found as a precipitate that formed when
extracts from nuclei were treated with
acid.
• Compound contained C, N, O, and high
amount of P.
• Was an acid compound found in nuclei
therefore named nucleic acid
Nucleic Acids
• 1944 Oswald, Avery, MacLeod and
McCarty demonstrated that DNA is
the molecule that carrier genetic
information.
• 1953 Watson and Crick proposed
the double helix model for the
structure of DNA
Nucleic Acids
• Nucleic acids are long polymers of
nucleotides.
• Nucleotides contain a 5 carbon sugar, a
weakly basic nitrogenous compound
(base), one or more phosphate groups.
• Nucleosides are similar to nucleotides
but have no phosphate groups.
Pentoses of Nucleotides
• D-ribose (in RNA)
• 2-deoxy-D-ribose (in
DNA)
• The difference - 2'OH vs 2'-H
• This difference affects
secondary structure
and stability
Nitrogenous Bases
Bases are attached by b-Nglycosidic linkages to 1 carbon of
pentose sugar – (Nucleoside)
Nucleosides
• Base is linked via a b-Nglycosidic bond
• The carbon of the glycosidic
bond is anomeric
• Named by adding -idine to
the root name of a pyrimidine
or -osine to the root name of
a purine
• Conformation can be syn or
anti
• Sugars make nucleosides more
water-soluble than free
bases
Anti- conformation
predominates in nucleic acid
polymers
Nucleotides
• Phosphate ester of nucleosides
The plane of the base is oriented
perpendicular to the plane of the
pentose group
Other Functions of
Nucleotides
• Nucleoside 5'-triphosphates are
carriers of energy
• Bases serve as recognition units
• Cyclic nucleotides are signal molecules
and regulators of cellular metabolism
and reproduction
• ATP is central to energy metabolism
• GTP drives protein synthesis
• CTP drives lipid synthesis
• UTP drives carbohydrate metabolism
• Nucleotide monomers are joined by 3’-5’
phosphodiester linkages to form nucleic acid
(polynucleotide) polymers
Nucleic Acids
• Nucleic acid backbone takes on
extended conformation.
• Nucleotide residues are all oriented
in the same direction (5’ to 3’)
giving the polymer directionality.
• The sequence of DNA molecules is
always read in the 5’ to 3’ direction
Bases from two adjacent DNA
strands can hydrogen bond
•Guanine pairs with
cytosine
•Adenine pairs with
thymine
Base pairing evident in
DNA compositions
H-bonding of adjacent antiparallel
DNA strands form double helix
structure
Properties of DNA Double Helix
• Distance between the 2 sugar-phosphate backbones
is always the same, give DNA molecule a regular
shape.
• Plane of bases are oriented perpendicular to
backbone
• Hydrophillic sugar phosphate backbone winds around
outside of helix
• Noncovalent interactions between upper and lower
surfaces of base-pairs (stacking) forms a closely
packed hydrophobic interior.
• Hydrophobic environment makes H-bonding between
bases stronger (no competition with water)
• Cause the sugar-phosphate backbone to twist.
View down the Double Helix
Hydrophobic
Interior with base
pair stacking
Sugar-phosphate
backbone
Structure of
DNA Double
Helix
• Right handed helix
• Rise = 0.33
nm/nucleotide
• Pitch = 3.4 nm /
turn
• 10.4 nucleotides
per turn
• Two groves – major
and minor
• Within groves,
functional groups on
the edge of base
pairs exposed to
exterior
• involved in
interaction with
proteins.
Factors stabilizing DNA
double Helix
• Hydrophobic interactions – burying
hydrophobic purine and pyrimidine rings
in interior
• Stacking interactions – van der Waals
interactions between stacked bases.
• Hydrogen Bonding – H-bonding between
bases
• Charge-Charge Interactions –
Electrostatic repulsions of negatively
charged phosphate groups are minimized
by interaction with cations (e.g. Mg2+)