Case Western Reserve University Organic Chemistry 4th Edition Paula Yurkanis Bruice Chapter 27 Nucleosides, Nucleotides, and Nucleic Acids I Irene Lee Case Western Reserve University Cleveland, OH ©2004, Prentice Hall

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

ATP as a Chemical Energy Source The energy released from ATP hydrolysis is used to drive the phosphorylation of D-gluose (coupled reactions)

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 3. Greater resonance stabilization 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