Lecture Twelve : Nucleic Acids and DNA

Convener : Dr. Fawaz Aldabbagh

First Year Organic Chemistry

Biological Chemistry

Two Nucleic Acids (Polymers) – deoxyribonucleic acid (DNA) and

ribonucleic acid (RNA)

Mild degradation yields monomeric units Nucleotides

Complete degradation

yields

1. A Heterocyclic Base

2. A five Membered Monosaccharide

3. A Phosphate ion

Pyrine or Pyrimidine

D-Ribose or 2-deoxy-D-ribosePO

O

O

O

O

OH OH

NH2COP

O

OH

HO1'

2'3'

4'

5'

Heterocyclic Base

N- Glycosidic linkage

RNA - Nucleotide

O

OH H

NH2COP

O

OH

HO1'

2'3'

4'

5'

Heterocyclic Base

N- Glycosidic linkage

DNA - Nucleotide

The Phosphate ester can be at C-5’ or C-3’

Hydolysis of Phosphate

Nucleoside

N

N N

N

NH2

H

O

H Guanine

(G)

N

N N

N

NH2

H Adenine

(A)

Purines

N

N

O

H

O

Thymine (DNA only) (T)

N

N

NH2

Cytosine

(C)

Pyrimidines

O

H3C

H H

N

N

O

H

O

Uracil (RNA only) (U)

H

Tautomerism (see Keto-Enol Tautomerism notes)

Simultaneous shift of a proton and a pair of electrons

N

N N

N

NH2

H

N

N

O

H

O

H

N

N N

N

NH

H H

N

N N

N

NH

H

H

N

N N

N

NH

H

H

Predominant

Predominant

N

N

OH

O

H

N

N

OH

OH

Nucleosides that can be obtained from DNA

N

NN

N

NH2

O

HOH

HH

HH

HO

NH

N

N

O

NH2N

O

HOH

HH

HH

HO

O

HOH

HH

HH

HO

N

N

NH2

O

2'-Deoxyadenosine 2'-Deoxyguanosine

2'-Deoxycytidine 2'-Deoxythymidine

O

HOH

HH

HH

HO

HN

N

O

O

Nucleosides that can be obtained from RNA

N

NN

N

NH2

O

OHOH

HH

HH

HO

NH

N

N

O

NH2N

O

OHOH

HH

HH

HO

O

OHOH

HH

HH

HO

N

N

NH2

O

Adenosine Guanosine

Cytidine Uridine

O

OHOH

HH

HH

HO

HN

N

O

O

Nucleotides are held together by phosphate ester linkages.Phosphate esters link 3’- OH of one ribose (or deoxyribose) with the 5’-OH of another. This makes the nucleic acid a long unbranched chain with a backbone of sugar and phosphate units with heterocyclic bases protruding from the chain at regular intervals.

N

NN

N

NH2

O

HO

HH

HH

PO

O

O

O

HO

HH

HH

HN

N

O

O

O

PO

O

NH

N

N

O

NH2N

O

HO

HH

HH

O

PO

O

O

Adenine

Thymine

Guanine

3'

5'

5'

3'

3'

5'

A T G5' 3'

Base Sequence is the Genetic Code

Primary Structure

Secondary Structure

N

N

O

O

H

H3C

N

N N

NN

H

H

Thymine

Adenine

N

N

N

O

N

N N

N

Cytosine

GuanineNH

H

O

H

H

H

Two Complementary Chains Result

E. Chargaff

Double Helix is the Secondary Structure of DNA

Two nucleic acid chains are held together by weak H-bonds between bases of opposite strands

Wound into a helix with a common axis

The base pairs are on the inside of the helix and the sugar-phosphate backbone is on the outside

34A repeating unit contains 10 successive nucleotide pairs

Phosphate-Sugar backbone is regular, base pairs can assume many different permutations

Watson-Crick Model of

DNA (1953)

Replication of DNA

Just prior to cell division the double strands of DNA begin to unwindComplementary Strands are formed along each chainEach chain acts in effect as a template for the formation of its complementWhen unwinding and duplication are complete, there are two identical DNA molecules where only one had existed before These two molecules can then be passed on, one to each daughter cell

A Gene is the segment in DNA, which contains the necessary information to direct the synthesis of one protein

RNA is a single-stranded molecule, thus RNA unlike DNA does not contain equal amounts of specific basesRNA molecules are much smaller than DNA

RNA can fold back on itself to give double helical regions, if complementary regions along an RNA strand exist

Synthetic Nucleic Acid Bases in Medicine

                                                                                               

1988, Nobel Prize for MedicineProfessor Sir James Black

Gertrude Elion and George Hitchings

Inhibitors of Nucleic Acid Synthesis

N

N N

N

NH2

N

N N

N

SH

H H6-Mercaptopurine

Adenine

Treatment of leukemia

pseudonucleotides

NH

NH

O

5-Fluorouracil

F

O NH

NH

O

H3C

O

Thymine

Treatment of Breast Cancer

N

N N

N

O

Acyclovir (Herpes viruses)

O

OH

H

H2N