Spring 2020 - CHEM 459 D200
Special Topics in Organic Chemistry (3)
Class Number: 2067
Delivery Method: In Person
Course Times + Location:
Mo, We, Fr 12:30 PM – 1:20 PM
WMC 3255, Burnaby
Exam Times + Location:
Apr 19, 2020
12:00 PM – 3:00 PM
TAKE HOME-EXAM, Burnaby
Prerequisites:CHEM 380 with a minimum grade of C-, or permission of the instructor.
An advanced, in-depth treatment of a specialized area of organic chemistry.
1 tutorial hour/week - Monday, 1:30PM-2:20PM
Course description: This modular survey course will introduce students to modern topics in chemical biology with an emphasis on applications of organic chemical principles to biological research and biotechnology. The course is divided into three modules as follow:
The topics to be covered in the lectures will include synthetic and biosynthetic strategies used to produce derivatives of the major classes of biomolecules (nucleic acids, proteins, carbohydrates). Examples of chemical probes used in imaging, chemical genetics, and non-traditional methods for manipulating the levels and activities of biomolecules will be described. Examples of major experimental advances accomplished using these methods and tools will be described. Emphasis will be placed on current and classic papers in the primary literature as well as critical review of recent research papers. Though not required, owing to the interdisciplinary nature of the subject matter of this course, students will benefit from an introductory-level understanding of biochemistry as well as cell and molecular biology.
COURSE-LEVEL EDUCATIONAL GOALS:
Literature discussions: The reading of scientific literature is an essential skill for scientists in all sectors; government, private, and academic. One aim of this course will be to improve skill at reading the literature through practice and discussion. Classes will therefore involve discussion of assigned literature including one paper per week. The articles will be circulated in class for the following week. Prior to class discussion prepare a concise write-up in which you answer the assigned questions. During class discussion we will briefly analyze the assigned paper and evaluate connections to the lecture material.
Topics covered in each course module:
Module 1: Introduction to chemical biology – synthesis and biosynthesis of biomolecules
- What is chemical biology?
- General structure of cells and cell theory
- Introduction to cell cycle
- Transient interactions enable biology
- Revisiting the central dogma of molecular biology
- Chemical biology of nucleic acids
- Structure and properties of DNA and RNA
- Revisiting replication and transcription
- Roles of synthetic DNA in molecular biology
- Introducing unnatural nucleobases into nucleic acids
- Chemical biology of proteins
- Amino acids and proteins – structures and properties
- Introduction to translation
- Post-translational modifications
- Methods to synthesize peptides and unnatural proteins
- Chemical biology of glycoconjugates
- Structure and properties of glycoproteins and glycolipids
- Biosynthesis of glycosidic linkages
- Methods to globally manipulate glycans
- Chemical synthesis of oligosaccharides
- Developments in DNA sequencing
- Dideoxy sequencing
- Next and Third Generation sequencing methods
- Select uses of DNA sequencing in directed evolution, biology, and DNA encoded libraries
- Genome editing
- Strategies and concepts for molecular evolution
- Introduction to combinatorial strategies to identify new molecular properties
- Selections and screens
- Directed evolution in vitro and in vivo
- DNA templated libraries
- Chemical approaches to identifying targets and gene function
- Forward and reverse chemical genetics – target based and phenotypic screening
- Combinatorial libraries, DNA encoded libraries, Diversity Oriented Synthesis
- Methods for target identification
- Linking gene to gene function using chemical tools
- Controlling proteins using small molecules
- Introduction to detecting biomolecules in cells and in vivo
- Basic principles of photophysics
- Fluorescence and fluorescence imaging methods (FRAP, FLIP, FRET, FLIM)
- Positron emission tomography
- Detecting biomolecules in cells using chemical biology
- Proteins – genetically encoded fluorescent tags and small molecule labeling methods
- Nucleic acids – genetically encoded tags and small molecule labeling methods
- Glycans – metabolic engineering and small molecule labeling methods
- Detecting small molecules and enzyme activity in cells using chemical biology
- Enzyme substrates, activity based proteomic probes, genetically encoded sensors
- Improved fluorophores, quantum dots, nanoparticle quenching, luminescent molecules
- Super resolution microscopy, STED, localization methods, and photoswitching
- Small molecule sensors, photopharmacology
- Problem Sets 10%
- Discussion Write-ups and Participation 40%
- Module Exams 50%
Grades for the course will be based on an average of the grades from each module. Each module will be graded based on the above.
Lectures will be based largely on the primary literature and the following text by Profs. Van Vranken & Weiss at UC Irvine:
- Van Vranken, D. L. & Weiss, G. A. Introduction to Bioorganic Chemistry and Chemical Biology
Additional reading is highly recommended for students particularly those with limited background in introductory biochemistry, biological chemistry, and molecular and cell biology. The following books are either available on-line at the PubMed bookshelf or have been requested to be on reserve in the Bennett library. Some can be found on the PubMed bookshelf (online).
- Alberts, B. A., et al. Molecular Biology of the Cell (4th edition and onward).
- D. Voet and J.G. Voet, Biochemistry, (3rd edition and onward).
- Blackburn, G.M & Gait, M.J. Nucleic Acids in Chemistry and Biology (2006 edition)
- Varki, A., et al. Essentials of Glycobiology, (2009) (available on-line)
Department Undergraduate Notes:
A grade of C- or better is required for all prerequisite courses.
SFU’s Academic Integrity web site http://www.sfu.ca/students/academicintegrity.html is filled with information on what is meant by academic dishonesty, where you can find resources to help with your studies and the consequences of cheating. Check out the site for more information and videos that help explain the issues in plain English.
Each student is responsible for his or her conduct as it affects the University community. Academic dishonesty, in whatever form, is ultimately destructive of the values of the University. Furthermore, it is unfair and discouraging to the majority of students who pursue their studies honestly. Scholarly integrity is required of all members of the University. http://www.sfu.ca/policies/gazette/student/s10-01.html
ACADEMIC INTEGRITY: YOUR WORK, YOUR SUCCESS