Bioengineering 315 --- Biochemical and Molecular Bioengineering

Instructor: Dan Ratner and Valerie Daggett

Credits: 3

UW General Catalog Course Description:
Introduction to the requisite organic, physical and biochemistry for incoming bioengineers to understand biological systems at the molecular level. Bioen 315 will establish a molecular scale foundation for the bioengineering core curriculum.

Prerequisites:
CHEM 223 or 237; BIOL 180. Co-requisite: BIOL 200.

Overview:

The chemistry of living systems is composed of discrete molecular species that can be chemically defined and engineered at the molecular level. ‘Biochemical and Molecular Bioengineering,’ (BMB) will train incoming Bioengineering students in the necessary organic and biochemistry to understand and appreciate the biological systems studied in the core curriculum at the molecular level. This course will draw concrete connections between Bioe prerequisites and the core classes in bioengineering. Specific areas of study will include: (1) Organic Functionality in Biochemistry (Carbonyl group, esters, amides, phosphates (phosphodiesters), acetal/hemiacital, amines, thiols, alcohols (nucleophiles) carboxylates), review stereochemistry, review nucleophilicity, hydrogen bonding; (2) Biomolecular structure and function (DNA, protein, lipids, carbohydrates); (3) Enzymology, chemical driving force behind enzymes, Gibbs free energies, transition states, catalysis, specific enzymes (synthases, proteases, nuclease, glycosidase, lipase, gpi biosynthesis example), enzyme kinetics; (4) Bioconjugate techniques for the chemical modification of biomolecules (activated ester/amide chemistry, thiol chemistry, reductive amination, periodate modification, homo/hetero-bifunctional cross-linkers, click chem.); (5) and molecular engineering and current problems in biomedical engineering and research. Bioen 315 will focus heavily on tools for the molecular-scale engineering of biochemical systems, and establish a basic organic, physical and biochemical understanding of biological systems.

Textbook:
Bioen 315 will use a course packet developed using materials from relevant scholarly literature in organic chemistry, biochemistry and bioconjugate chemistry.  This course packet can also serve as a reference for other Bioengineering Courses.  Select excerpts from texts including, “Biochemistry” by Voet and Voet, “Organic Chemistry” by Solomons, and “Bioconjugate Techniques” by Hermanson.

Learning Objectives:
At the end of this course, students will:

• Be able to identify the major organic functional groups associated with biomolecules (e.g. hydroxyl, amino, amide, ester, thiol, ether, carboxylate, imine, phosphate, sulfate).
• Understand the reactivities of biomolecules (nucleophilicity, electrophilicity, pKa, acid/base) and the formation/hydrolysis of common bonds in biomolecules (peptide, phosphodiester, glycosyl).
• Be able to describe the driving forces and energetics associated with biomolecular processes (free energy, energy diagrams, enthalpy, entropy)
• Be familiar with the structure and chemical nature of the major biomolecules (DNA, Protein, Carbohydrate, Lipid).  Students will be able to recognize the common biomolecules (i.e. the individual amino acids, carbohydrates, nucleic acids and lipids), and know their chemical properties.
• Be able to describe the techniques used for coupling biomolecules through organic transformations of reactive side-chains on proteins, nucleic acids and carbohydrates (NHS chemistry, maleimide chemistry, disulfide conjugations, homo- and heterobifunctional crosslinking).  Students should be able to propose the synthesis of bioconjugates used for vaccines, drug design and biomaterials.
• Students should be able to synthesize the aforementioned knowledge and apply these concepts to current problems in biomedical engineering and research.

Course Grading:
The course grade will be determined by two midterm examinations (40%), weekly homework assignments (30%), short essay projects (10%) and a final examination (20%).

Course Topics:

Week	Lecture Topics
1	Organic Chemistry for Bioengineers – ‘SPONCH and stuff’ Bonding (notation, delocalization) Biochemical functional group chemistry
2	Chemical reactivity in biological systems Acid/bases, pKa, nucleophiles, electrophiles Formation and hydrolysis of esters and amides
3	Physical Chemistry in biology and organic chemistry Free energies, energy of systems and energy diagrams Molecular interactions (electrostatic, Van der Waal, hydrogen bonding) Structure of water
4	Central Dogma of Biochemical Systems (Intro and Logic to Bioen 315 approach) DNA (Structure, Function, Mol. Biol.
5	Proteins Protein composition (AA->Peptide) Protein structure (1°->2°->3°->quaternary)
6	Driving forces in biomolecular structure (P-chem) Functional roles of proteins (Enzymes, structure, drugs and drug targets) Intro/refresher to enzymes and enzymology [NOTE: Bioen 317 Enzyme Kinetics Lab in week 6 or 7]
7	Carbohydrates – structure and Function Biological roles played by carbohydrates (protein/lipid modification, adhesion)
8	Lipids – structure and function (membranes) Biological roles of lipids, cholesterol and lipoconjugates (gpi, LPS, glycolipids)
9	Bioconjugate chemistry Chemical modification of DNA and proteins Chemical modification of carbohydrate and lipids
10	Biomedical applications for molecular engineering Bioconjugate drug and vaccine design Surface engineering for biomaterials and medical devices