* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download The Chemistry of Life
Transcriptional regulation wikipedia , lookup
Synthetic biology wikipedia , lookup
Cell-penetrating peptide wikipedia , lookup
Expanded genetic code wikipedia , lookup
Silencer (genetics) wikipedia , lookup
Maurice Wilkins wikipedia , lookup
Community fingerprinting wikipedia , lookup
Gene expression wikipedia , lookup
Gel electrophoresis of nucleic acids wikipedia , lookup
DNA vaccination wikipedia , lookup
Genetic code wikipedia , lookup
Molecular cloning wikipedia , lookup
Molecular evolution wikipedia , lookup
Point mutation wikipedia , lookup
Non-coding DNA wikipedia , lookup
List of types of proteins wikipedia , lookup
DNA supercoil wikipedia , lookup
Biochemistry wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Vectors in gene therapy wikipedia , lookup
Cre-Lox recombination wikipedia , lookup
The Chemistry of Life The Age of the Molecule, Roy. Soc. Chem. 1999. p. 229-258 1 • 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 2 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). 3 Simvastatin O OH O O O H 고지혈증 치료제, 200억불/20조원 ( 82억불- 10조원/ 년-2002년 Pfizer-리피토) (62억불-MSD-Zocor-2002년) –Sonata 150만대 4 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. 5 Gerhard Domagk- the First Antibacterial drug (septicemia- 패혈증). 1927 6 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. 7 • 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. 8 9 10 Life Expectancy 11 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 12 Protein Structures Primary structure Secondary structure Tertiary structure b-sheet a-helix reverse turn 5/ 31/ 05 첨단화학 13 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. 14 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 15 Drug Action enzyme (rest state) normal signal activated enzyme false signal inactivated enzyme 16 Structure of DNA Building blocks 17 RNA 18 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. 19 Bases pairing via HB RNA (ribonucleic acid) 20 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. 21 Biosynthesis of Proteins Cell 22 Genetic Code 4 x 4 x 4 = 64 combinations Triplet sequences of nucleotide bases Codon-Rosetta Stone 23 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). 24 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 25 Anticancer Drugs 26 27 • 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… 28 Antiviral Drugs AZT (Zidovudine) Wellcome,1987 George Hitchins, 1988 Nobel Prize Medicine HIV virus 29 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. 30 Future challenges for Chemistry in Biology and Medicine Penicillin, Aspirin, Simvastatin 31 반응메커니즘 (Reaction MechanismMultimedia) 32