24CHM115_spring_09 - 1 CHM 11500 Lecture 23 Drugs as...

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Unformatted text preview: 1 CHM 11500 Lecture 23 Drugs as Molecules External readings; p. 732; pp 698- 699 See the course website 2 Drugs as Molecules Identification Molecular Mechanism of Diseases (Cancer, Parkinsons, Alzheimers) Identify proteins (Enzymes or receptors) that malfunction causing the disease (Target identification) Search for organic molecules (Drugs) that can bind to target proteins and prevent the malfunction 3 Parkinsons Disease Neurodegenerative movement disorder caused by the death of dopaminergic neurons in the substantia niagra pars compacta Affects 700,000 - 1 million people in US Second most common neurodegenerative disorder after Alzheimers disease ~10% early-onset (diagnosed before age 50) Age is greatest risk factor: affects ~1% of the population over age 65 Those afflicted with PD include: Pope John Paul II Muhammad Ali Michael J. Fox 4 Gene Genetics Biochemical Function -Synuclein Dominant (A30P, A53T, Triplication) Unknown Parkin Recessive (Nonsense mutations, Deletions) E3 Ligase UCH-L1 Polymorphism (S18Y) Ubiquitin Hydrolase Ubiquitin Ligase(?) DJ-1 Recessive (L166P, Deletions) Molecular Chaperone Pink I Recessive (Nonsense truncations, G306D) Unknown Ser/Thr kinase (?) LRRK2 Dominant (Y1699C, R1441C, I1122V, I2020T) Kinase (?) Genes Mutated in PD 5 What are the ways we treat cancer? Surgery Physical removal of cancerous tumor Radiation Chemotherapy Destroys all rapidly dividing cells that includes cancer cells, but also Cells in your hair (hair loss) Bone marrow (fatigue) Stomach lining (nausea) Biologic therapies 6 Chemotherapy-based approaches to stopping cancer growth If we know what causes the cancer to form in the first place, it may be possible to create a drug that will stop it from happening EXAMPLE: chronic myeloid leukemia (CML) and Gleevec 7 The Bcr-Abl protein: the cause of Chronic Myeloid Leukemia (CML) Part of the bcr-abl protein Alpha-Helices! Beta- sheets 8 http://www.youtube.com/watch?v=QR6d2cfImRc&feature=PlayList&p=51B0065F084908ED&index=1&playnext=2&playnext_from=PL http://www.youtube.com/watch?v=iaK99RxEyAU&feature=PlayList&p=51B0065F084908ED&index=0 9 Gleevec: a bcr-abl inhibitor Bcr-abl is a phosphorylating agent: it adds phosphorous to proteins that dont want phosphorous to behave normally! Source of the cancer Gleevec prevents the substrate from binding, so phosphorylation cant occur, and cancer doesnt form 10 question 1 Gleevec What are the main intermolecular forces that Gleevec uses to bind to bcr-abl?...
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This note was uploaded on 02/06/2012 for the course CHM 115 taught by Professor Towns during the Spring '08 term at Purdue University-West Lafayette.

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24CHM115_spring_09 - 1 CHM 11500 Lecture 23 Drugs as...

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