Course syllabus for Chemistry 162A / 262A Drug Design (Fall 2012) Class meets: Mon, Wed, Fri 12:00 – 12:50 Phelps 1444 Instructor: Professor Kalju Kahn, Office: PSB-N 2623 E-mail: [email protected] Phone: (805) 893-6157 Office Hours: Tue 11:30-12:30, Thu 12:30-1:30 or by appointment Course website: http://www.chem.ucsb.edu/~kalju/chem162 Lecture Textbook: Richard B. Silverman, The Organic Chemistry of Drug Design and Drug Action, 2nd edition Graham L. Patrick, An Introduction to Medicinal Chemistry, 4th edition (optional) The Course: In Chem 162 students learn principles that govern the process of modern drug discovery and development. Students will follow a path similar to that taken by real-life drug developers by learning important elements of the drug design process in a logical order. Some topics that we focus more extensively in 162A are:  Target identification and validation  Receptor mechanisms and receptor targeting  Chemical libraries and screening  Ligand-based drug design Expectations of Students:  Attendance and taking good lecture notes is expected. Submitting completed assignments in time is required.  The textbook provides some necessary background material. Furthermore, students are expected to read modern drug design-related research literature. Required literature will be available on the course website.  Honesty and academic integrity must be always preserved. While discussing your ideas with others is encouraged outside the classroom, you must answer the assignment questions individually. No supplemental material should be used during an exam.  Your grade in the course is based on points you collect from the weekly assignments (10 points each), the mid-term (40 points), the final exam (50 points), and the written research proposal (50 points). Grading will be based on the curve but you have to meet a certain level to get a grade higher than F.  The course requires that you have a solid understanding of basic biology and organic chemistry; good background in biochemistry and physical chemistry will be very helpful.  No student shall give, sell, or otherwise distribute to others or publish any electronically available course materials or recordings made during any course presentation without the written consent of the instructor. Study tips:  I am posting lecture note slides on-line before the class meets so that you can focus on following my talk. The slides are mainly illustrative and you need to follow the lecture in order to fully understand the topics I cover.  Come in class prepared. Read the relevant textbook material and required reading before the class meets. I like to interact with students during our meetings and you enjoy the lectures more if you can think along.  Review (or rewrite) your class notes the same day and supplement them with material from the textbook and other resources (optional reading, Internet). Ask for help if something remains unclear.  This course is not about memorization of names, reactions, or facts. It is about understanding the process, its principles and methods. You should demonstrate good understanding of the material when answering assignment questions and the exam problems. Your creativity and originality are highly important for getting a high score in the final written proposal. Good luck! — KaljuChem162/262 Schedule for the Winter 2011 Jan 9 M Overview and history of drug design Jan 11 W Rational drug design: overview of approaches Jan 13 F Current trends and future of drug design. Diseases. Jan 16 M Martin Luther King, Jr.'s Birthday Jan 18 W Target identification and validation: Principles First assignment due Jan 20 F Target validation: Pre-genomic methods Jan 23 M Target validation: Post-genomic methods Jan 25 M Target validation: Bioinformatics Second assignment due Jan 27 W Tutorial in the computer lab (Chem 1153): Target identification from microarray data Jan 30 M Receptors as drug targets: Overview of biosignaling Feb 1 W Receptors as drug targets: Ion channels Third assignment due Feb 3 F Receptors as drug targets: G-protein coupled receptors Feb 6 M Experimental characterization of membrane-bound receptors Feb 8 W Nuclear hormone receptors Feb 10 F Tutorial in the computer lab (Chem 1153): Analysis of estrogen receptor Feb 13 M Chemical libraries and combinatorial chemistry Feb 15 W Principles of assay development Fourth assignment due Feb 17 F High-throughput screening for lead identification Feb 20 M Presidents’ day Feb 22 W Midterm Exam Feb 24 F General strategies for lead optimization Feb 27 M Ligand-based drug design and optimization Feb 29 W Ligand-based drug design and optimization Fifth assignment due Mar 2 F Ligand-based drug design and optimization Mar 5 M Fragment-based drug design and optimization Mar 7 W Tutorial in the computer lab (Chem 1153): Ligand building and modeling Mar 9 F QSAR: Overview Mar 12 M QSAR: Technical Details Sixth assignment due Mar 14 W Tutorial in the computer lab (Chem 1153): (Chem 1153): Practical QSAR Mar 16 F Course Review and Evaluation Written draft proposals due Assignments 1. Diseases and targets 2. Target validation: literature work 3. Target validation: microarray analysis 4. Receptors: general features and mechanisms 5. Pharmacophores and molecular similarity 6. Molecular properties, ligand-based