Chem 224
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Chem 224
Bioorganic Chemistry Fall 2014 T, Th 8:10 – 9:25 AM Room SC 1308, Stevenson Center (SC, Math) |
Carmelo Rizzo |
updated: 11/15/2014
Tentative Course Content
I. Amino Acids, Peptides, and Proteins
A. Amino acid structure, properties, chemical synthesis, and analysis
B. Peptide and Protein: structure, synthesis, and analysis
C. Combinatorial Libraries
II. Enzymes Mechanisms
A. Catalytic sidechains – proteases, phosphotases
B. Cofactors
III. Nucleosides, Nucleotides and Nucleic Acids
Prerequisite: Chem 220 a and b (Organic Chemistry)
Text: There is NO required text for this course. Exams and assignments will come entirely from class notes. The bookstore has the following recommended texts:
Chemical Approaches to the Synthesis of Peptides and Proteins, P. Lloyd-Williams, F. Albericio, E. Giralt, CRC Press, Boca Raton,1997. ISBN 0-8493-9142-3
An Introduction to Enzyme and Coenzyme Chemistry (3rd ed),T.D.H. Bugg, Wiley, New York, 2012, ISBN: 1119995949
Nucleic Acids in Chemistry and Biology (3rd ed), G. Michael Blackburn, Michael J. Gait, David Loakes, and David Williams, Royal Society of Chemistry Publishing, 2006, ISBN: 978-0-85404-654-6
The following is an excellent review on peptide ligation and combinatorial chemistry and is highly
recommended. You can download a pdf version free of charge from a computer with a Vanderbilt IP
address.“Synthesis of Native Proteins by Chemical Ligation” Dawson, P. E.; Kent, S. B. H. Annu. Rev.
Biochem. 2000, 69, 923-960.“Synthesis and Applications of Small Molecule Libraries.” Thompson, L. A.; Ellman, J. A. Chem.
Rev. 1996, 96, 555-600.The following is an excellent resource on peptide masss spectrometry and is available as an ebook
through ACORN:“Overview of Peptide and Protein Analysis
by Mass Spectrometry,” Carr, S. A.; Annan, R. S. Curr Protoc Protein Sci. 2001 Chapter 16: Unit 16.1.“Introduction to Proteomics: Tools for the New Biology,” Liebler, D. C., Human Press: 2002
Exams: Three mid term exams – see class schedule for dates.
Grading: Each exam with count equally toward the final grade. Graduate students are also required to write a short paper (10 page limit) on a topic of their choice (with approval from me), related to bioorganic chemistry. In addition, they will present a short lecture (15 minutes) on their topic. You should choose a topic by Oct. 27.
Office hours: open – you can stop by anytime you like. It might be best to let me know in advance that you are planning to drop in.
Questions & Answers Page: I am posting questions and answers from the class, sent to me
via email.
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Tentative class schedule |
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| Thur., Aug. 21 | Amino acids: Struture, acid-base chemistry, and chemical synthesis
The Medical Biochemistry Page (by Prof. Michael W. King, Univ. of Indiana, School of Medicine) |
amino acidsslides 1-49 (revised 9/6/2012)amino acid acid/base chemistry problems |
| Tue., Aug. 26 | Solid-phase peptide synthesis: Protecting groups, coupling reagents, and the solid support
“Solid-Phase Peptide Synthesis: A Silver Anniversary Report,” Barany, G.; Kneib-Cordonier, N.; Mullen, D. G. Int. J. Peptide Protein Res. 1897, 30, 705-739. “Chemical Synthesis of Peptides and Proteins,” Kent, S.B.H. Ann Rev Biochem.1988, 57, 957-989 “Amino Acid-Protecting Group,” Isidro-Llobet, A.; Alvarez, M.; Albericio, F. Chem. Rev. 2009, 109, 2455-2504. |
Peptide synthesis problem set (answers) |
| Thur., Aug. 28 | Solid-phase peptide syntheis (con’t): | |
| Tue., Sept. 2 | Solid-phase peptide syntheis (con’t): Native peptide ligation; cyclic peptides
“Synthesis of Native Proteins by Chemical Ligation” Dawson, P. E.; Kent, S. B. H. Annu. Rev. Biochem. 2000, 69, 923-960. “Contemporary Strategies for Peptide Macrocyclization,” White, C. J.; Yudin, A. K. Nature Chem. 2011, 3, 509-524. |
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| Thur., Sept. 4 | Protein Structure: Amino acid analysis and peptide sequencing
“Introduction to Proteomics: Tools for the New Biology,” Liebler, D. C., Human Press: 2002 available as an ebook through ACORN. |
slides 50-84 (revised 9/12/2013) |
| Tue., Sept. 9 | Protein Structure: Methods of protein structure determination | slides 85-113 (revised 9/12/2013) |
| Thur., Sept. 11 | Protein Structure: Hydrogen bonds, the hydrophobic effect, α-helices, β-sheets, β-turns | Biomolecular Turorial |
| Tue., Sept. 16 | Combinatorial Synthesis
“Synthesis and Applications of Small Molecule Libraries.” Thompson, L. A.; Ellman, J. A. Chem. Rev. 1996, 96, 555-600. |
slides 114-138 (revised 8/15/2013) |
| Thur., Sept. 18 | Enzyme Chemistry- catalysis, proteases | slides 139-187 (revised 9/24/2014) |
| Tue., Sept. 23 | First Hour Exam | |
| Thur., Sept. 25 | Enzyme Chemistry- phosphatases | |
| Tue., Sept. 30 | Cofactor Chemistry- Thiamin and pyridoxal dependent enzymes | |
| Thur., Oct. 2 | Cofactor Chemistry- Pyridoxal dependent enzymes | (mid-semester dificiency report due) |
| Tue., Oct. 7 | Cofactor Chemistry- Nicotinamide dependent enzymes | |
| Thur., Oct. 9 | Cofactor Chemistry- Flavin dependent enzymes | slides 188-241 (revised 9/23/2013) |
| Tue., Oct. 14 | Cofactor Chemistry- Flavin dependent enzymes | |
| Oct. 16 – 17 | October Break- no class | cofactor mechanism problems (answers) |
| Tue., Oct. 21 | Cofactor Chemistry- Heme and Vitamin B12 dependent enzymes | |
| Thur., Oct. 23 | Structure and Properties of Nucleosides, Nucleotides and Nucleic Acids (History of DNA) | slides 242-369 (revised 11/15/2014) |
| Tue., Oct. 28 | Second Hour Exam | Graduate student term paper topics due |
| Thur., Oct. 30 | DNA Processing Enzymes: DNA polymerases, ligases, restriction endonucleases, PCR, site-directed mutagenesis | DNA replication animation |
| Tue., Nov. 4 | Nucleoside and Solid-phase oligonucleotide synthesis; DNA sequencing | |
| Thur., Nov. 6 | Nucleotide Biosynthesis | |
| Tue., Nov. 11 | Nucleoside Analogues as Therapeutic Agents | |
| Thur., Nov 13 | Nucleic Acids as Therapeutic Agents, siRNA | RNAi animation |
| Tue., Nov. 18 | RNA & Translation; DNA Damage & Repair | Transcription animation |
| Thur., Nov. 20 | Third Hour Exam | |
| Nov. 22-30 | Thanksgiving Break – no classes | |
| Tue., Dec. 3 | Graduate Student Presentations (no class for the undergraduates) | |
| Thur., Dec. 5 | Graduate Student Presentations (no class for the undergraduates) | term papers due for graduate students |
Exams from Spring 2000:
| Exam 1Answers |
Exam 2Answers |
Exam 3Answers |