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Chapter 27

Nucleosides,
Nucleotides,
and
Nucleic Acids I


Irene Lee
Case Western Reserve University
Cleveland, OH
©2004, Prentice Hall
Organic Chemistry
4th Edition
Paula Yurkanis Bruice
Nucleic Acids
In nucleic acid, the phosphate group is phosphodiester
The Bases in Nucleic Acids
Adenine, guanine, cytosine, and thymine are found in
DNA
Adenine, guanine, cytosine, and uracil are found in RNA
Nucleosides = Base + Sugar
Nucleotides = Base + Sugar + Phosphate
Different Forms of Nucleotides
The energy released from ATP hydrolysis is used to drive
the phosphorylation of D-gluose (coupled reactions)
ATP as a Chemical Energy Source
Breakage of the Phosphoanhydride Bond in ATP
Without ATP, the OH– group cannot be displaced
This reaction does not occur without ATP because of the
poor leaving group
Phosphoryl Transfer Reaction Mechanism I
Phosphoryl Transfer Reaction Mechanism II
Phosphoryl Transfer Mechanism III
Pyrophosphate can be further hydrolyzed to phosphate
Why is the hydrolysis of a phosphoanhydride bond so
exergonic?
1. Greater electrostatic repulsion in ATP
2. More solvation in the products
The interactions between ATP, Mg2+, and arginine and
lysine residues at the active site of an enzyme
Since all the negative charges in ATP are neutralized,
ATP is readily approached by nucleophiles
Other Important Nucleotides
Cyclic AMP serves as a link between several hormones
and certain enzymes that regulate cellular function
The Nucleic Acids
Biosynthesis of DNA
occurs in the 5’ 3’
direction
Complementary Base Pairing in DNA
The sugar–phosphate is on the outside, and the bases
are on the inside
The DNA Double Helix
Hydrolysis of RNA
The Three Helical Forms of DNA
Hydrogen bonding and base stacking interactions hold
the DNA helix together
Replication of DNA
Transcription of DNA
A stretch of bases representing a portion of a gene is
called an exon
A stretch of bases that contain no genetic information is
called an intron
mRNA is spliced prior to leaving the nucleus
A Transfer RNA
The Proposed Mechanism for
Aminoacyl-tRNA Synthetase
The Substrate-Binding Site for tRNAHis
A protein is synthesized from its N-terminal end to its
C-terminal end
Each amino acid is specified by a three-base sequence
known as the genetic code
Translation
Why does DNA contain thymine instead of uracil?
The synthesis of thymine is energetically expensive
Because cytosine can be converted to uracil ….
Having T’s in place of U’s in DNA allows the U’s that are
found in DNA to be recognized as mistakes
DNA Sequencing
Laboratory Synthesis of DNA
Oligonucleotide
Synthesis with
Phosphoramidites
The amino groups of the bases must be protected
Removal of the Protecting Group by Ammonia
Utilization of H-phosphate
monomer to synthesize DNA strand
Hoogsteen Base Pairing
1 Organism -> more than 105
genetically-controlled Functions
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UNIFR
Rusconi
2002
Molecular diagnosis : microarrays
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UNIFR
Rusconi
2001
Functional genomics:
current impact on research
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Good:
Financial availability of microarray services & tools
Possibility to tackle functional gene patterns alterations
Novel hypotheses on primary and subsequent responders (infections, stresses, stimuli, drugs, development)
UNIFR
Rusconi 2002
Bad:
too deterministic interpretation blocks understanding
too many research teams join in the `fashion field`
insufficient attention and understanding on the mechanistic aspects (real time kinetics)
Functional genomics current impact on clinics
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UNIFR
Rusconi 2002
clinical experimental leukemia profiling
early clinical assessment of pharmacogenomics principles
strong interest of pharmaceutical companies
increasing interest of practicting clinicians