The Chemistry of Life

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The Chemistry of Life
The Age of the Molecule, Roy. Soc. Chem. 1999.
p. 229-258
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• Friedrich Wöhler in 1828 showed that urea, an
  organic compound, could be made(converted) from
  a salt ( inorganic ) mineral.

mid-1800s no more vitalistic theory
today no clear distinction between organic and
inorganic chemistry unified chemistry but,
all organic chemicals contain the element carbon
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Herbal/ Microorganism-derived Medicines
1500 BC- Ebers papyrus.????- ???, ?????-
??, ??London Pharmacopoeia,1809 (Unknown at
the Molecular level).
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The First Synthetic Drug

• Methylene Blue (Dye)- Malaria, 1891
• Paul Ehrlich The first person to use
  synthetic comd. as a drug-the Magic Bullet
  concept.
• infectious disease, parasite disease.

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Gerhard Domagk- the First Antibacterial drug
(septicemia- ???). 1927
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Wonderful Penicillins

• Alexander Fleming- Antibacterial activity
• found of Penicillium notatum (1928).
• Oxford Group- H. Florey, E. Chain, Clinical
  trial, chemical identification -1941, World War
  II. (1945? ?????)
• American group- Scale-up production Penicillium
  chrysogenum.

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• Stereochemistry of the chemical structure of Pen
  G.- Dorothy Hodgkin.Oxford U.(1945).
• 1964? ?????.
• First synthesis-John Sheehan (M.I.T.), 1957.
• Eli Lilly-Penicillin V Semisynthsis Orally
  active.
• The supreme achievements of Drugs in 20th
  C.-Penicillin, Aspirin.

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Life Expectancy
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Proteins- Workhorses of life

• 1930???- Protein random aggregates of amino
  acids by amide bonds.
• X-ray crystallography alpha-helix??(Linus
  Pauling, Caltech.).
• Amino acid sequences??- Frederick Sanger
  (Cambridge U.) 1945. ????? 2? ??
• Myoglobin, haemoglobin? 3D-?? ??? - folds, the
  alpha-helix, beta sheet.(X-ray??). John Kendrew
  (Cambridge U.)-1958?. ?????

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Protein Structures
Primary structure
Secondary structure
Tertiary structure
b-sheet
reverse turn
a-helix
5/ 31/ 05 ????
Chemistry
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• The first enzyme, Lysozyme? X-ray?? ??- David
  Phillips-( Oxford U.) 1968.
• ?????? ???? ???-Solid Phase Synthesis
  ribonuclease??(124 amino acids, ?? 17 yield)???
  - Bruce Merrifield (Rockefeller U.) 1969.
• Almost Life processes Interactions of Proteins
  with Small organic molecules.( hormones,
  neurotransmitters, vitamins, carcinogens).
• ???? ????? ???. Binding? ????.
• Proteins enzyme catalyst of biochemical
  reactions or receptors of cell membranes.

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The Adrenaline cascade
Fear fight hormone. Lock Key type Binding -
Emil Fischer
Why do different stereoisomers have different
biological properties?
A chiral molecule must fit into a chiral receptor
at some target site to exert its biological
action.
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Drug Action
normal signal
enzyme (rest state)
activated enzyme
false signal
inactivated enzyme
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Structure of DNA
Building blocks
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RNA
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James Watson Francis Crick (1953)Discovery of
DNA double helix
Structure how DNA could replicate itself. how
genetic information be stored/ transmitted.Unwind
s each strand blueprint for production of a new
strand.
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Bases pairing via HB
RNA (ribonucleic acid)
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Genetic Code

• DNA provides the blueprint(genetic information)
  to RNA (messenger-RNA), in turn provide the
  genetic code for protein/enzyme production, and
  thus establishes the hierarchy of the cell.

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Biosynthesis of Proteins
Cell
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Genetic Code
4 x 4 x 4 64 combinations Triplet sequences
of nucleotide bases - Codon-Rosetta Stone
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Rise of Genetic Engineering

• Restriction enzymes that could cut DNA at
  specific sites.
• S. Cohen at Stanford used DNA ligase and
  Restriction enzymes to cut and join DNA from two
  different organisms to generate the first
  recombinant DNA.
• Determination of the natural DNA sequence to
  construct DNA to order.
• Genome Sequences- the complete sequences of genes
  in cells nucleus (human genomes).

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Role of DNA in Drug Design

• Structure Function of DNA benefits in drug
  design.
• The endpoint of drug molecule-receptor complexes
  activation or repression of DNA replication or
  transcription.- Drug Design

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Anticancer Drugs
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• Organic (nonmetal) Elements and Life

- the Organic elements found in living
organisms - carbon compounds

• - DNA, RNA, amino acid, proteins, lipid,
  carbohydrates
• medicine, dyes, polymers, plastics, food
  additives,
• pesticides, fragrant

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Antiviral Drugs
HIV virus
AZT (Zidovudine)Wellcome,1987 George
Hitchins, 1988 Nobel Prize Medicine
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Chemistry and Gene Therapy

• GDEPT
• Gene Directed Enzyme-activiated
• Prodrug Therapy(GDEPT) resulted inhibition of
  DNA replication.
• The Role of Chemists
• Design highly specific Prodrugs and novel
  Delivary systems.

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Future challenges for Chemistry in Biology and
Medicine

• Penicillin, Aspirin, Simvastatin

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