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Chemistry 569: Advanced Bioorganic Chemistry

Course Level: 
Graduate Level
Academic Year: 
2017/2018

General Description:  This course is designed to introduce senior chemistry students with little or no background in biochemistry to the techniques and theories of modern bioorganic chemistry.  Much of the course will focus on understanding the chemical strategies and mechanisms behind enzyme catalysis. 

 Key concepts in the biosynthesis of natural products and the design of enzyme inhibitors will also be presented.  Students will also be exposed to "special topics" that have recently appeared in the literature such as the use of bioorthogonal reagents and the development of new catalysts.  Although not absolutely essential, it is strongly recommended that students have taken either Chem313 or Chem330 as a prerequisite.

Recommended Text:  No text is required for the course, but it is strongly recommended that students either purchase or consult one of the following books (available at Woodward library).
1) An Introduction to Enzyme and Coenzyme Chemistry by Tim Bugg
2) The Organic Chemistry of Enzyme-Catalyzed Reactions by Richard Silverman

Examinations:  For Chem413 students there will be one midterm (35%) and the final exam (65%).  For graduate students enrolled in Chem569 there will be one midterm (25%), the final exam (55%), and a take home essay-style assignment (20%).

Instructor: Prof. Martin E. Tanner, A241 Chem./Phys. Building, 

Office hours: M-Th afternoons by appointment and scheduled prior to exams.  E-mail questions will be answered if brief.

Outline:

Intro:  Structure of enzymes, folding forces, active sites

Enzymatic catalysis: transition state binding, strategies for catalysis

Enzyme kinetics:  Michaelis-Menten kinetics, inhibition kinetics, kinetic isotope effects

Cofactor-independent isomerases/dehydratases: triose phosphate isomerase (TIM), concept of perfect enzyme, isotope exchange, intermediate release, glutamate racemase, fumarase

Hydrolases:  proteases, oxyanion hole, covalent catalysis, burst kinetics, transition state analogs
glycosidases, 2-fluoro-sugars, (special topic: glycosynthases), phosphatases

Ligases/transferases: ATP activation, tyrosine kinases (special topic: bump-and-hole), glycosyltransferases (special topic: bioorthogonal reagents)

Oxidation-reduction:  NAD+/NADH, dehydrogenases, transient oxidation, FAD/FADH2, UDP-galactose mutase, positional isotope exchange.

Cofactor-independent C-C bond formation/cleavage: aldolases, decarboxylases, terpene cyclases

Non-Redox Cofactors: pyridoxal phosphate (PLP), irreversible inhibition, thiamine pyrophosphate (TPP), S-adenosyl methionine (SAM), tetrahydrofolate (THF)

Related Topics - Time Permitting

Biosynthesis: polyketide synthases (special topic: biosynthetic engineering of unnatural natural products), non-ribosomal peptide synthases, terpene biosynthesis, alkaloid biosynthesis

DNA Chemistry: structure of DNA, DNA catalysis (special topic: selections for DNA catalysts)

Protein splicing: native chemical ligation