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Biochem 704 - Chemical Biology
Spring 2007-2008
A 2-credit graduate-level course (30 sessions) on the use of ideas and methods of chemistry to solve problems in molecular and cell biology. The course is organized around the flow of information in biological systems, and emphasizes how chemists can intervene at each step, both to elucidate and control that flow. A major goal is to
empower both chemists and biologists by providing chemists with relevant new targets and biologists with useful new tools.
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Course Materials |
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Course Description:
Section 001
(Class Number: 51364
)
| Instructor(s): |
Kiessling,Laura Lee; Raines,Ronald T.; Weibel,Douglas B |
| TA(s): |
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| Credits: |
2
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| Day: |
TR
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Time: |
09:55 AM - 10:45 AM
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| Location: |
Rm 175 BCHM ADDN
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Website: |
http://www.biochem.wisc.edu/courses/biochem704
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Description:
Course Description
Biochemistry 704: “Chemical Biology” is a 2-credit graduate-level course (30 sessions) on the use of ideas and methods of chemistry to solve problems in molecular and cell biology. The course is organized around the flow of information in biological systems, and emphasizes how chemists can intervene at each step, both to elucidate and control that flow. A major goal is to empower both chemists and biologists by providing chemists with relevant new targets and biologists with useful new tools.
Prerequisites
Successful completion of courses in organic chemistry (e.g., Chemistry 343 and 345 at Wisconsin), biochemistry (e.g., Biochemistry 501), physical chemistry (Chemistry 561 or 565) is assumed. You should already be able to answer questions such as
a. Draw the mechanism (using curved arrows to indicate electron flow) for the reaction of acetone and ammonia to form
CH3–C(=NH)–CH3 (an imine or “Schiff base”) and water.
b. Write the expression for the rate of product formation (v = ∂[B]/∂t) during the chemical reaction:
c. Draw the molecular structure of each natural amino acid and nucleobase.
If you are not familiar with the above material (especially, question a), you should not register for this course.
Grades
Grades will be based on in-class participation (20%), problem sets and quizzes (20%), an original research proposal (50%), which will be assessed during in-class “study sections”, and reviews of two other research proposals during the in-class study sections (5% + 5%).
Texts
No text is required, but the following could be helpful references.
Copies are available in the Steenbock Library.
Alberts, B. et al. Molecular Biology of the Cell. Routledge (2007)
Blackburn, G. M. et al. Nucleic Acids in Chemistry and Biology. Royal Society of Chemistry (2006)
Frey, P. A. & Hegeman, A. D. Enzymatic Reaction Mechanisms. Oxford University (2006)
Grossman, R. B. The Art of Writing Reasonable Organic Reaction Mechanisms. Springer (2007)
Jencks, W. P. Catalysis in Chemistry and Enzymology. Dover (1987)
McMurry J. & Begley, T. The Organic Chemistry of Biological Pathways. Roberts & Co. (2005)
Voet, D. & Voet, J. G. Biochemistry. John Wiley & Sons (2004)
Website
www.biochem.wisc.edu/courses/biochem704/
View
Syllabus as Calendar
| Date | Event Information |
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1/22/2008
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Information Flow in Chemistry and Biology
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Type:
Class
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Instructor: Kiessling
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1/24/2008
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DNA Synthesis
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Type:
Class
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Course Material
Reading Fodor et al. - Science 1991, 251, 767 - 773 Singh-Gasson et al. - Nat. Biotechnol. 1999, 17, 974 - 978
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1/29/2008
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DNA Structure
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Type:
Class
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Instructor: Kiessling
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Course Material
Homework Problem Set 1 (Assigned: 1/29/2008 - Due: 2/5/2008) Reading Hirao - Curr. Opin. Chem. Biol. 2006, 10, 622 - 627 Moran et al. - Proc. Natl. Acad. Sci. USA 1997, 94, 10506 - 10511 Piccirilli et al. - Nature 1990, 343, 33 - 37
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1/31/2008
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DNA Recognition
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Type:
Class
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Instructor: KIessling
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Course Material
Handout DNA Recognition PDF; 4 slides/page DNA Recognition PowerPoint Reading Dervan - Bioorg. Med. Chem. 2001, 9, 2215 - 2235 Garvie & Wolberger - Mol. Cell 2001, 8, 937 - 946 Jones et al. - J. Mol. Biol. 1999, 287, 877 - 896
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2/5/2008
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Special Guest Lecture
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Type:
Class
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Guest Lecturer: Prof. Sarah O'Connor (MIT)
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Course Material
Handout O'Connor PowerPoint O'Connor slides; 4 slides/page Homework Problem Set 1 (Assigned: 1/29/2008 - Due: 2/5/2008)
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2/7/2008
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DNA Recognition (continued)
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Type:
Class
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Instructor: Kiessling
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Course Material
Reading Ansari & Mapp - Curr. Opin. Chem. Biol. 2002, 6, 765 - 772 Brent & Ptashne - Cell 1985, 43, 729 - 736 Frankel & Kim - Cell 1991, 65, 717 - 719 Hertzberg & Dervan - J. Am. Chem. Soc. 1982, 104, 313 - 315 Sigman et al. - Chem. Rev. 1993, 93, 2295-2316
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2/12/2008
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RNA Structure and Folding; RNAi
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Type:
Class
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Instructor: Raines
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Course Material
Handout RNA Structure PowerPoint RNAi movie Reading Fire - Angew. Chem. Int. Ed. 2007, 46, 6966 - 6984 Mello - Angew. Chem. Int. Ed. 2007, 46, 6985 - 6994
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2/14/2008
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RNA Synthesis; Transcription and its Modulation by Small Molecules
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Type:
Class
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Instructor: Raines
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Course Material
Handout Transcription PowerPoint Reading Biggins et al. - ChemBioChem 2007, 8, 799 - 803 Shevde et al. - Proc. Natl. Acad. Sci. USA 2002, 99, 13487 - 13491 Swann et al. - J. Am. Chem. Soc. 2002, 124, 13795 - 13805
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2/19/2008
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RNA Aptamers; Ribozymes
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Type:
Class
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Instructor: Raines
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Course Material
Handout Molecular Evolution PowerPoint Homework Problem Set 2 (Assigned: 2/19/2008 - Due: 2/26/2008) Reading Altman - Angew. Chem. Int. Ed. 1990, 29, 749 - 758 Cech - Angew. Chem. Int. Ed. 1990, 29, 759 - 768 Doudna & Lorsch - Nat. Struct. Mol. Biol. 2005, 12, 395 - 402 Ellington & Szostak - Nature 1990, 346, 818 - 822 Tuerk & Gold - Science 1990, 249, 505 - 510 Werstuck & Green - Science 1998, 282, 296 - 298 Winkler & Breaker - Annu. Rev. Microbiol. 2005, 59, 487 - 517 Woese et al. - Proc. Natl. Acad. Sci. USA 1990, 87, 4576 - 4579
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2/21/2008
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Translation and its Modulation by Small Molecules
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Type:
Class
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Instructor: Raines
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Course Material
Handout Research Proposal Guidelines Ribosome Structure PowerPoint ribosome (Steitz) movie translation ("hippy") movie Reading Ban et al. - Science 2000, 289, 905 - 920 Hansen et al. - Proc. Natl. Acad. Sci. USA 2002, 99, 11670 - 11675 Nissen et al. - Science 2000, 289, 920 - 930 Schroeder & Wolfenden - Biochemistry 2007, 46, 4037 - 4044
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2/26/2008
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Translation and its Modulation by Small Molecules (continued)
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Type:
Class
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Instructor: Raines
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Course Material
Handout Ribosome Inhibitors PowerPoint ribosome (Yonath 1) movie ribosome (Yonath 2) movie Homework Problem Set 2 (Assigned: 2/19/2008 - Due: 2/26/2008) Problem Set 3 (Assigned: 2/26/2008 - Due: 3/4/2008) Reading Hansen et al. - Mol. Cell 2002, 10, 117 - 128 Schlünzen et al. - Nature 2001, 413, 814 - 821
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2/28/2008
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Peptide and Protein Synthesis; Protein Structure
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Type:
Class
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Instructor: Raines
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Course Material
Handout Protein Structure PowerPoint protein "roller coaster" movie Reading Bode et al. - Angew. Chem. Int. Ed. 2006, 45, 1248 - 1252 Dawson et al. - Science 1994, 266, 776 - 779 Hahn & Muir - Trends Biochem. Sci. 2005, 30, 26 - 34 Nielsen et al. - Science 1991, 254, 1497 - 1500 Nilsson et al. - Annu. Rev. Biochem. 2005, 34, 91 - 118
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3/4/2008
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Protein Folding and its Modulation by Small-Molecules
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Type:
Class
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Instructor: Raines
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Course Material
Handout Protein Folding PowerPoint Homework Problem Set 3 (Assigned: 2/26/2008 - Due: 3/4/2008) Problem Set 4 (Assigned: 3/4/2008 - Due: 3/11/2008) Reading Anfinsen et al. - Proc. Natl. Acad. Sci. USA 1961, 1309 - 1314 Brandts et al. - Biochemistry 1975, 14, 4953 - 4963 Creighton - J. Mol. Biol. 1977, 113, 275 - 293 Dill et al. - Protein Sci. 1999, 8, 1166 - 1180 Dill et al. - Protein Sci. 1995, 4, 561 - 602 Levinthal - J. Chim. Phys. 1968, 65, 44 - 45 Roder et al. - Nature 1988, 335, 700 - 704 Udgaonkar & Baldwin - Nature 1988, 335, 694 - 699 Weissman & Kim - Science 1991, 253, 1386 - 1393 Zwanzig et al. - Proc. Natl. Acad. Sci. USA 1992, 89, 20 - 22
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3/6/2008
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Protein Stability and its Modulation by Small Molecules
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Type:
Class
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Instructor: Raines
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Course Material
Handout Protein Stability PowerPoint Reading Balch et al. - Science 2008, 319, 916 - 919 Eilers & Schatz - Nature 1986, 322, 228 - 232 Hammarström et al. - Science 2003, 299, 713 - 716 Hill et al. - Science 1990, 249, 543 - 546 Pace - Trends Biochem. Sci. 1990, 15, 14 - 17 Regan & DeGrado - Science 1988, 241, 976 - 978 Shoichet et al. - Proc. Natl. Acad. Sci. USA 1995, 92, 452 - 456
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3/11/2008
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Protein Stability and its Modulation by Small Molecules (continued)
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Type:
Class
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Instructor: Raines
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Course Material
Homework Problem Set 4 (Assigned: 3/4/2008 - Due: 3/11/2008) Problem Set 5 (Assigned: 3/11/2008 - Due: 3/25/2008)
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3/13/2008
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Enzymatic Catalysis: Principles, Concepts, Targets
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Type:
Class
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Specific Aims Due
Instructor: Raines
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Course Material
Handout Enzymatic Proficiency PowerPoint Reading Hansen & Raines - J. Chem. Educ. 1990, 67, 483 - 489 Wolfenden & Snider - Acc. Chem. Res. 2001, 34, 938 - 945
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3/18/2008
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Spring Break
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Type:
No Class
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3/20/2008
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Spring Break
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Type:
No Class
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3/25/2008
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Enzymatic Catalysis: Principles, Concepts, Targets (continued)
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Type:
Class
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Instructor: Raines
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Course Material
Handout Linus Pauling PowerPoint Homework Problem Set 5 (Assigned: 3/11/2008 - Due: 3/25/2008) Reading Knowles - Nature 1991, 350, 121 - 124
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3/27/2008
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Enzymatic Catalysis: Principles, Concepts, Targets (continued)
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Type:
Class
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Instructor: Raines
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Course Material
Reading Highbarger & Gerlt - Biochemistry 1996, 35, 41 - 46
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3/30/2008
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Special Guest Lecture
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Type:
Class
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Guest Lecturer: Prof. Cathy Drennan (MIT)
Special Date and Time: Sunday at 4:00 pm
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4/3/2008
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Enzyme Inhibition in Vitro and in Cellulo
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Type:
Class
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Instructor: Raines
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Course Material
Handout Molecular Crowding PowerPoint Reading Burlingham & Widlanski - J. Chem. Educ. 2003, 80, 214 - 218 Cleland - Biochemistry 1975, 14, 3220 - 3224 Cravatt et al. - Annu. Rev. Biochem. 2008, 77, In Press Ellis - Trends Biochem. Sci. 2001, 26, 597 - 604 Myers & Widlanski - Science 1993, 262, 1451 - 1453 Raines & Hansen - J. Chem. Educ. 1988, 65, 757 - 759
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4/8/2008
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Non-Ribosomal Peptide Synthesis
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Type:
Class
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Instructor: Weibel
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4/10/2008
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Polyketide Synthesis
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Type:
Class
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Instructor: Weibel
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4/15/2008
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Signal Transduction and its Modulation by Small Molecules
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Type:
Class
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Research Proposal Due
Instructor: Kiessling
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Course Material
Handout Glycosylation PowerPoint neutrophil emigration movie neutrophil rolling movie Reading Helenius & Aebi - Annu. Rev. Biochem. 2004, 73, 1019 - 1049 O'Connor & Imperiali - J. Am. Chem. Soc. 1997, 119, 2295 - 2296 Werz et al. - ACS Chem. Biol. 2007, 2, 685 - 691
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4/17/2008
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Signal Transduction and its Modulation by Small Molecules
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Type:
Class
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Instructor: Kiessling
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4/22/2008
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Receptor - Ligand Engineering
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Type:
Class
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Instructor: Kiessling
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4/24/2008
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Receptor - Ligand Engineering
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Type:
Class
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Instructor: Kiessling
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Course Material
Reading Mayer et al. - Science 1999, 286, 971 - 974 Mitchison - Chem. Biol. 1994, 1, 3 - 6 Prescher & Bertozzi - Nat. Chem. Biol. 2005, 1, 13 - 21 Scheck & Francis - ACS Chem. Biol. 2007, 2, 247 - 251 Speers & Cravatt - Chem. Biol. 2004, 11, 535 - 546
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4/29/2008
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RESEARCH PROPOSAL-READING PERIOD
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Type:
Class
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5/1/2008
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STUDY SECTION
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Type:
Class
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Instructors: Kiessling/Raines/Weibel
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5/6/2008
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STUDY SECTION
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Type:
Class
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Instructors: Kiessling/Raines/Weibel
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5/8/2008
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STUDY SECTION
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Type:
Class
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Instructors: Kiessling/Raines/Weibel
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Course Materials
| | |
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Handout
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DNA Recognition PDF; 4 slides/page
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DNA Recognition PowerPoint
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Enzymatic Proficiency PowerPoint
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Glycosylation PowerPoint
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Linus Pauling PowerPoint
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Molecular Crowding PowerPoint
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Molecular Evolution PowerPoint
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|
O'Connor PowerPoint
|
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|
O'Connor slides; 4 slides/page
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Protein Folding PowerPoint
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Protein Stability PowerPoint
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Protein Structure PowerPoint
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RNA Structure PowerPoint
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RNAi movie
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Research Proposal Guidelines
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Ribosome Inhibitors PowerPoint
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Ribosome Structure PowerPoint
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Transcription PowerPoint
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neutrophil emigration movie
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neutrophil rolling movie
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protein "roller coaster" movie
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ribosome (Steitz) movie
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ribosome (Yonath 1) movie
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ribosome (Yonath 2) movie
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translation ("hippy") movie
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Homework
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Problem Set 1
(Assigned: 1/29/2008 - Due: 2/5/2008)
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Problem Set 2
(Assigned: 2/19/2008 - Due: 2/26/2008)
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Problem Set 3
(Assigned: 2/26/2008 - Due: 3/4/2008)
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Problem Set 4
(Assigned: 3/4/2008 - Due: 3/11/2008)
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Problem Set 5
(Assigned: 3/11/2008 - Due: 3/25/2008)
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Reading
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Altman
Angew. Chem. Int. Ed. 1990, 29, 749 - 758
|
|
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Anfinsen et al.
Proc. Natl. Acad. Sci. USA 1961, 1309 - 1314
|
|
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Ansari & Mapp
Curr. Opin. Chem. Biol. 2002, 6, 765 - 772
|
|
|
Balch et al.
Science 2008, 319, 916 - 919
|
|
|
Ban et al.
Science 2000, 289, 905 - 920
|
|
|
Biggins et al.
ChemBioChem 2007, 8, 799 - 803
|
|
|
Bode et al.
Angew. Chem. Int. Ed. 2006, 45, 1248 - 1252
|
|
|
Brandts et al.
Biochemistry 1975, 14, 4953 - 4963
|
|
|
Brent & Ptashne
Cell 1985, 43, 729 - 736
|
|
|
Burlingham & Widlanski
J. Chem. Educ. 2003, 80, 214 - 218
|
|
|
Cech
Angew. Chem. Int. Ed. 1990, 29, 759 - 768
|
|
|
Cleland
Biochemistry 1975, 14, 3220 - 3224
|
|
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Cravatt et al.
Annu. Rev. Biochem. 2008, 77, In Press
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Creighton
J. Mol. Biol. 1977, 113, 275 - 293
|
|
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Dawson et al.
Science 1994, 266, 776 - 779
|
|
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Dervan
Bioorg. Med. Chem. 2001, 9, 2215 - 2235
|
|
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Dill et al.
Protein Sci. 1999, 8, 1166 - 1180
|
|
|
Dill et al.
Protein Sci. 1995, 4, 561 - 602
|
|
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Doudna & Lorsch
Nat. Struct. Mol. Biol. 2005, 12, 395 - 402
|
|
|
Eilers & Schatz
Nature 1986, 322, 228 - 232
|
|
|
Ellington & Szostak
Nature 1990, 346, 818 - 822
|
|
|
Ellis
Trends Biochem. Sci. 2001, 26, 597 - 604
|
|
|
Fire
Angew. Chem. Int. Ed. 2007, 46, 6966 - 6984
|
|
|
Fodor et al.
Science 1991, 251, 767 - 773
|
|
|
Frankel & Kim
Cell 1991, 65, 717 - 719
|
|
|
Garvie & Wolberger
Mol. Cell 2001, 8, 937 - 946
|
|
|
Hahn & Muir
Trends Biochem. Sci. 2005, 30, 26 - 34
|
|
|
Hammarström et al.
Science 2003, 299, 713 - 716
|
|
|
Hansen & Raines
J. Chem. Educ. 1990, 67, 483 - 489
|
|
|
Hansen et al.
Proc. Natl. Acad. Sci. USA 2002, 99, 11670 - 11675
|
|
|
Hansen et al.
Mol. Cell 2002, 10, 117 - 128
|
|
|
Helenius & Aebi
Annu. Rev. Biochem. 2004, 73, 1019 - 1049
|
|
|
Hertzberg & Dervan
J. Am. Chem. Soc. 1982, 104, 313 - 315
|
|
|
Highbarger & Gerlt
Biochemistry 1996, 35, 41 - 46
|
|
|
Hill et al.
Science 1990, 249, 543 - 546
|
|
|
Hirao
Curr. Opin. Chem. Biol. 2006, 10, 622 - 627
|
|
|
Jones et al.
J. Mol. Biol. 1999, 287, 877 - 896
|
|
|
Knowles
Nature 1991, 350, 121 - 124
|
|
|
Levinthal
J. Chim. Phys. 1968, 65, 44 - 45
|
|
|
Mayer et al.
Science 1999, 286, 971 - 974
|
|
|
Mello
Angew. Chem. Int. Ed. 2007, 46, 6985 - 6994
|
|
|
Mitchison
Chem. Biol. 1994, 1, 3 - 6
|
|
|
Moran et al.
Proc. Natl. Acad. Sci. USA 1997, 94, 10506 - 10511
|
|
|
Myers & Widlanski
Science 1993, 262, 1451 - 1453
|
|
|
Nielsen et al.
Science 1991, 254, 1497 - 1500
|
|
|
Nilsson et al.
Annu. Rev. Biochem. 2005, 34, 91 - 118
|
|
|
Nissen et al.
Science 2000, 289, 920 - 930
|
|
|
O'Connor & Imperiali
J. Am. Chem. Soc. 1997, 119, 2295 - 2296
|
|
|
Pace
Trends Biochem. Sci. 1990, 15, 14 - 17
|
|
|
Piccirilli et al.
Nature 1990, 343, 33 - 37
|
|
|
Prescher & Bertozzi
Nat. Chem. Biol. 2005, 1, 13 - 21
|
|
|
Raines & Hansen
J. Chem. Educ. 1988, 65, 757 - 759
|
|
|
Regan & DeGrado
Science 1988, 241, 976 - 978
|
|
|
Roder et al.
Nature 1988, 335, 700 - 704
|
|
|
Scheck & Francis
ACS Chem. Biol. 2007, 2, 247 - 251
|
|
|
Schlünzen et al.
Nature 2001, 413, 814 - 821
|
|
|
Schroeder & Wolfenden
Biochemistry 2007, 46, 4037 - 4044
|
|
|
Shevde et al.
Proc. Natl. Acad. Sci. USA 2002, 99, 13487 - 13491
|
|
|
Shoichet et al.
Proc. Natl. Acad. Sci. USA 1995, 92, 452 - 456
|
|
|
Sigman et al.
Chem. Rev. 1993, 93, 2295-2316
|
|
|
Singh-Gasson et al.
Nat. Biotechnol. 1999, 17, 974 - 978
|
|
|
Speers & Cravatt
Chem. Biol. 2004, 11, 535 - 546
|
|
|
Swann et al.
J. Am. Chem. Soc. 2002, 124, 13795 - 13805
|
|
|
Tuerk & Gold
Science 1990, 249, 505 - 510
|
|
|
Udgaonkar & Baldwin
Nature 1988, 335, 694 - 699
|
|
|
Weissman & Kim
Science 1991, 253, 1386 - 1393
|
|
|
Werstuck & Green
Science 1998, 282, 296 - 298
|
|
|
Werz et al.
ACS Chem. Biol. 2007, 2, 685 - 691
|
|
|
Winkler & Breaker
Annu. Rev. Microbiol. 2005, 59, 487 - 517
|
|
|
Woese et al.
Proc. Natl. Acad. Sci. USA 1990, 87, 4576 - 4579
|
|
|
Wolfenden & Snider
Acc. Chem. Res. 2001, 34, 938 - 945
|
|
|
Zwanzig et al.
Proc. Natl. Acad. Sci. USA 1992, 89, 20 - 22
|
No homework assignments are currently due.
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