Ch440 – Advanced Biochemistry Prof. Ruben Savizky Email: rsavizky@cooper.edu Class Hours: Monday 9-12 (Room 106) Office Hours: Monday 12-1, Wednesday 12-1, Friday 11-12. I am usually in my office (Room 413) or in one of the labs on the 4th floor, but the best times to find me are right before or after class. If you would like to set up an appointment just email me. Texts: Berg, J. M., Tymoczko, J. L., and Stryer, L., Biochemistry, 6th ed., W.H. Freeman and Company, New York, 2006 Mikkelsen, S. R. and Cortón, E., Bioanalytical Chemistry, Wiley and Sons, Hoboken, 2004 Silverman, R. B., The Organic Chemistry of Drug Design and Drug Action, 2nd ed., Elsevier, 2004 These books will be supplemented by readings/excerpts from other biochemistry textbooks, as well as from journal articles from the primary scientific literature. Prerequisites: Ch232, Ch340 (or permission of instructor) Suggested courses: Bio101, Bio102, Ch251, Ch262 Recommended additional material: This course will assume a basic understanding/knowledge of biology and organic chemistry. Here are some supplementary textbooks that may be helpful: Solomons, Organic Chemistry Watson, Molecular Biology of the Cell Campbell, Biology These are excellent (more advanced) resources for more information: Voet and Voet, Biochemistry (2nd ed.) Van Holde, K. E., Johnson, W. C. and Ho, P. S., Principles of Physical Biochemistry, 2nd ed., Pearson Prentice Hall, Upper Saddle River, 2006 Cantor, C. R. and Schimmel, P. R., Biophysical Chemistry Part II: Techniques for the Study of Biological Structure and Function, W. H. Freeman and Company, New York, 1980 Tentative Schedule: “The best-laid schemes o' mice an' men / Gang aft agley” – Robert Burns, "To a Mouse, on Turning Her Up in Her Nest with the Plough" (1785) Date 1/17 Topic Introduction to Bioanalytical Chemistry HW#1: Sasakura, K. et al, J. Am. Chem. Soc., 2011, 133, 18003-18005 Qian, Y. et al, Nature Comm., 2011,2(495), 1-7 Chapter(s) Mikkelsen, Chapter 1 1/23 Validation of Bioanalytical Techniques HW#2: Hori, S. S. and Gambhir, S. S., Sci. Trans. Mikkelsen, Chapter 16 1/30 Med., 2011, 3(109), 1-9 Palacios, M. A. et al, Proc. Nat. Acad. Sci. USA, 2011,108(40), 16510-16514 Antibodies and Immunoassays HW#3: Kelkar, S. S. and Reineke, T. M., Bioconjugate Chem., 2011, 22, 1879-1903 Stryer, Chapter 3 and Mikkelsen, Chapter 5 Stryer, Chapter 8 and Mikkelsen, Chapter 3 Stryer, Chapters 8 and 9 and Silverman, Chapter 5 2/5 Enzymes 2/12 Enzyme Inhibition and Inactivation HW#4: Nomura, D. K. et al, Science, 2011, 334, 809813 Duggan, K. C. et al, Nature Chem. Biol., 2011,7, 803809 2/26 Membrane Channels and Pumps HW#5: Vedula, L. S. et al, J. Biol Chem., 2011, 284(36), 24176-24184 Nury, H. et al, Nature, 2011, 469, 428-433 Stryer, Chapter 13 3/5 Signal Transduction Pathways HW#6: Chung, K. Y. et al, Nature, 2011, 477, 611-617 Westfield, G. W. et al, Proc. Nat. Acad. Sci USA, 2011, 108(38), 16086-16091 Stryer, Chapter14 3/19 3/26 Student Presentations – Bioanalytical Techniques 4/2 4/9 4/16 Metabolism overview Stryer, Chapter 15 Drug Discovery, Design and Development Stryer, HW#7: Visnyei. et al, Mol. Cancer Ther., 2011, 10(10), Chapter 35 and 1818-1828 Silverman, Xie, J. et al, J. Am. Chem. Soc., 2011,133, 13946-13949 Chapter 2 Structure-Activity Relationships Silverman, Chapter 2 HW#8: Perales, J. B. et al, Bioorg. Med. Chem. Lett., 2011, 21, 2816-2819 Yuan, J. et al, Science, 2011,333, 724-729 DNA-Interactive Agents HW#9: Thomas, J. R. and Hergenrother, P. J., Chem Rev., 2008, 108(4), 1171-1224 Stryer, Chapters 4 and 28 and 4/23 Drug Metabolism 4/30 Prodrugs and Drug Delivery Systems HW#10: Namanja, H. A. et al, J. Am. Chem. Soc., 2011, ASAP, A-E Walsh. et al, ACS Nano., 2011,5(7), 5427-5432 5/4 Student presentations – Original Grant Proposal Silverman, Chapter 6 Silverman, Chapter 7 Silverman, Chapter 8 Course layout: The class will consist of lectures on these various topics. There will be ten homework assignments and two projects. Homework: Homework will consist of journal summaries. You will have a week to complete the assignment. Generally, it will be collected and graded. The journal article summaries will attempt to show you applications of the concepts. For the critiques, you will be given an article (or two) from the biochemical literature and will be given one week to read it(them). You will also be expected to write a short (2-5 page) summary, which should include a brief synopsis of the paper(s), the significance, as well as the pros and cons of the experiment/technique/approach. We will then discuss the paper(s) in class the following week. Project 1: Description of a bioanalytical technique In lieu of a midterm exam you will be asked to research and describe a bioanalytical technique. You may choose from the following suggestions: fluorescence polarization, FRET, size exclusion chromatography, hydrodynamic chromatography, dynamic light scattering, biomarkers, catalytic antibodies, SELEX, yeast two-hybrid systems, capillary electrophoresis, isoelectric focusing, MALDI TOF MS, FT-ICR MS, VCD, TIRF microscopy, FISH, ITC, DSC, photoacoustic calorimetry, surface plasmon resonance, NOESY, TROSY, MAD X-ray diffraction, CARS. You can also choose something not on the list, pending my approval. Each student should present a different bioanalytical technique. I will pass around a sheet for each student to list his/her topic in class. For this project you will be asked to write a report as well as give an oral presentation. Your report should contain the basic elements of a technical paper: abstract, introduction, procedure, results, conclusion, and references. You will also be expected to do an oral presentation (approximately 10-15 minutes) of your work. Project 2: Grant proposal In lieu of a final exam you will be asked to write a final paper, in the form of an original research proposal. You may choose something related to any of the topics that will be covered, or something that we have not talked about. In either case you will need to get my approval. Of primary importance is that your idea be unique (though it certainly can be based on the work of others). Your proposal should contain the basic elements of a technical paper: abstract, introduction, procedure, results, conclusion, and references. You will also be expected to do an oral presentation (approximately 10-15 minutes) of your work. Your proposal should abide by the National Science Foundation (NSF) Grant Proposal Guidelines (GPG), which I will provide as a .pdf file. Please be sure to read this thoroughly. As an example, you may consider your proposal to be for a Cellular Processes solicitation under the Molecular and Cellular Biosciences (MCB) division of the Directorate for Biological Sciences (BIO). The synopsis of this solicitation is copied below: (http://nsf.gov/funding/pgm_summ.jsp?pims_id=503612&org=MCB&from=home) The Cellular Processes Cluster encourages the use of innovative approaches and technologies that resolve long-standing questions in cell biology. The cluster seeks to support imaginative projects that integrate research on processes at the supramolecular and cellular scales. The cluster recognizes the need for rigorous, quantitative approaches for cell biology and welcomes multidisciplinary research that includes physical, mathematical, and computational approaches. Areas of particular interest include livecell imaging, single-particle analysis of macromolecular assemblies, architectural organization and dynamics of structures over broad dimensional scales. This cluster entertains proposals in the following general areas of cell biology: Membrane organization and function Organelle biogenesis, maintenance, and trafficking Cytoskeletal dynamics, cell division and motility Remember that plagiarism is a serious offense. Please make sure you make appropriate citations and reference the works you use. Plagiarism includes copying words AND ideas/concepts. For example if someone else comes up with a hypothesis or explanation you have to say something like "Smith proposes ...". You cannot imply that it was your hypothesis or explanation. If I feel you have plagiarized you will receive a grade of 0 for the assignment. Grades: Your grade will be determined as follows: Homework: 40% Project 1: 30% (Report 20%, Oral Presentation 10%) Project 2: 30% (Report 20%, Oral Presentation 10%)