Download The Chemistry of Life

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.
NH4+ -OCN
Ammonium cyanate
heat
H2N
O
C
NH2
Urea
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Herbal/ Microorganism-derived
Medicines
1500 BC- Ebers papyrus.
本草綱目- 이시진, 명
東醫寶鑑- 허준, 조선
London Pharmacopoeia,1809
(Unknown at the Molecular level).
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Simvastatin
O
OH
O
O
O
H
고지혈증 치료제,
200억불/20조원 ( 82억불- 10조원/ 년-2002년
Pfizer-리피토) (62억불-MSD-Zocor-2002년)
–Sonata 150만대
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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- 패혈증). 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. (1945년 노벨의학상)
• American group- Scale-up production
Penicillium chrysogenum.
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• Stereochemistry of the chemical structure of
Pen G.- Dorothy Hodgkin.Oxford U.(1945).
1964년 노벨화학상.
• 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
• 1930년까지- Protein : random aggregates of
amino acids by amide bonds.
X-ray crystallography : alpha-helix구조(Linus
Pauling, Caltech.).
Amino acid sequences결정- Frederick Sanger
(Cambridge U.) 1945. 노벨화학상 2번 수상
Myoglobin, haemoglobin의 3D-구조 결정됨 folds, the alpha-helix, beta sheet.(X-ray이용).
John Kendrew (Cambridge U.)-1958년. 노벨화
학상
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Protein Structures
Primary structure
Secondary structure
Tertiary structure
b-sheet
a-helix
reverse turn
5/ 31/ 05 첨단화학
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Chemistry
The first enzyme, Lysozyme의 X-ray구조 결정David Phillips-( Oxford U.) 1968.
구조결정으로 유기합성 시작됨-Solid Phase
Synthesis ribonuclease효소(124 amino acids,
전채 17% yield)합성함 - Bruce Merrifield
(Rockefeller U.) 1969.
Almost Life processes : Interactions of Proteins
with Small organic molecules.( hormones,
neurotransmitters, vitamins, carcinogens).
단백질이 작은분자를 둘러쌈. Binding과 촉매작용.
Proteins: enzyme catalyst of biochemical
reactions or receptors of cell membranes.
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The Adrenaline cascade
HO
OH
HO
Fear fight hormone.
Lock & Key type Binding - Emil Fischer
NH
CH 3
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.
C
C
Mismatched
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Drug Action
enzyme
(rest state)
normal
signal
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.
Unwinds 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 cell’s 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
H
C N O F
Si P S Cl
Br
I
- DNA, RNA, amino acid, proteins, lipid, carbohydrates…
-medicine, dyes, polymers, plastics, food additives,
-pesticides, fragrant…
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Antiviral Drugs
AZT (Zidovudine)
Wellcome,1987
George Hitchins,
1988 Nobel Prize
Medicine
HIV virus
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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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반응메커니즘
(Reaction MechanismMultimedia)
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