1. 1 The Chemistry of Life The Age of the Molecule, Roy. Soc. Chem. 1999. p. 229-258

2. 2 Friedrich Wöhler in 1828 showed that urea, an “ o rganic “ compound, could be made(converted) fro m 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

3. 3 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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5. 5 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.

6. 6 Gerhard Domagk- the First Antibacterial drug (septicemia- 패혈증 ). 1927

7. 7 Alexander Fleming- Antibacterial activity found of Penicillium notatum (1928). Oxford Group- H. Florey, E. Chain, Clinical trial, chemical identification -1941, World War II. (1945 년 노벨의학상 ) American group- Scale-up production Penicillium chrysogenum. Wonderful Penicillins

8. 8 Stereochemistry of the chemical structure of Pen G.- Dorothy Hodgkin.Oxford U.(1945). 1964 년 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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11. 11 Life Expectancy

12. 12 Proteins- Workhorses of life 1930 년까지 - Protein : random aggregates of amino acids by amide bonds. X-ray crystallography : alpha-helix 구조 (Linus Pauling, Caltech.). Amino acid sequences 결정 - Frederick Sanger (Cambridge U.) 1945. 노벨화학상 2 번 수상 Myoglobin, haemoglobin 의 3D- 구조 결정됨 - folds, the alpha-helix, beta sheet.(X-ray 이용 ). John Kendrew (Cambridge U.)-1958 년. 노벨화학상

13. 13 Protein Structures Protein Structures  -helix reverse turn  -sheet Primary structure Secondary structure Tertiary structure Chemistry 5/ 31/ 05 첨단화학

14. 14 The first enzyme, Lysozyme 의 X-ray 구조 결정 - David Phillips-( Oxford U.) 1968. 구조결정으로 유기합성 시작됨 -Solid Phase Synthesis ribonuclease 효소 (124 amino acids, 전 채 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. Binding 과 촉매작용. Proteins: enzyme catalyst of biochemical reactions or receptors of cell membranes.

15. 15 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. Mismatched Fear fight hormone. Lock & Key type Binding - Emil Fischer The Adrenaline cascade

16. 16 enzyme (rest state) normal signal activatedenzyme inactivatedenzyme false signal Drug Action

17. 17 Structure of DNA Building blocks

18. 18 RNA

19. 19 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.

20. 20 Bases pairing via HB RNA (ribonucleic acid)

21. 21 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.

22. 22 Biosynthesis of Proteins Biosynthesis of Proteins Cell

23. 23 Genetic Code 4 x 4 x 4 = 64 combinations Triplet sequences of nucleotide bases - Codon-Rosetta Stone

24. 24 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).

25. 25 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

26. 26 Anticancer Drugs

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28. 28 - the Organic elements found in living organisms - carbon compounds - DNA, RNA, amino acid, proteins, lipid, carbohydrates… -medicine, dyes, polymers, plastics, food additives, -pesticides, fragrant… Organic (nonmetal) Elements and Life

29. 29 Antiviral Drugs AZT (Zidovudine) Wellcome,1987 George Hitchins, 1988 Nobel Prize Medicine HIV virus

30. 30 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.

31. 31 Future challenges for Chemistry in Biology and Medicine Penicillin, Aspirin, Simvastatin

32. 32 반응메커니즘 (Reaction Mechanism-Multimedia)