Chem 162B/262B
Drug Design
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Chem 162B/262B |
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Dr. Kalju Kahn
Office: PSB-N 2623
Office hours: Tue 3:30-4:30 PM, and Thu 3:30-4:30 PM
Phone: 893-6157
E-mail: kalju@chem.ucsb.edu
Website: http://www.chem.ucsb.edu
To teach principles that govern the process of modern drug discovery and development. Students in the course 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. The course is taught in two different quarters as 162A and 162B but students are welcome to take 162B/262B without taking Chem 162A/262A first.
Chem 162A starts with an overview of principles of rational drug design. Topics covered include target identification and validation technologies, generation and screening of chemical libraries for finding lead compounds, and modern medicinal chemistry approaches for ligand-based lead optimization. We will cover membrane-bound ion-channels and receptor proteins, and discuss strategies for finding agonists and antagonists for these types of targets.
Chem 162B focuses on structure-based drug design. Students taking this course will become familiar with the basic principles that govern biological recognition in ligand-protein complexes, and learn to appreciate how the knowledge of the three-dimensional structure of the active site helps in the lead optimization process. Chem 162B will also cover approaches used to design competitive and mechanism-based inhibitors through the mechanistic understanding of enzyme catalysis. Finally, issues of pharmacokinetics and drug metabolism will be dealt with, and the rationale behind prodrugs and drug delivery systems will be analyzed.
Lecture: MWF 12:00-12:50 Place: Phelps Hall 1444
Computer Lab: Open day access Place: Chem 1153
| Syllabus | General information about the course. | |
| Textbook | The Organic Chemistry of Drug Design and Drug Action by Richard B. Silverman (Second Edition) | Amazon |
| Last Years | Drug Design 162A (by Dr. Kalju Kahn) website for Fall 2009 | Link |
| Last Years | Drug Design 162B (by Dr. Kalju Kahn) website for Spring 2009 | Link |
| Exam | Midterm Preparation Guide | |
| Exam | Midterm Key | |
| Exam | Final Exam Preparation Guide | |
| Upload | Submit your assignments as PDF files | Link |
Course notes will be posted here before 7:30 a.m. of the lecture day. The lecture slides are password-protected. Contact your instructor to obtain the password.
| Notes | Lecture Notes. Powerpoint Pages in PDF | Acrobat |
| Jan 4 | Overview of the course. Review of Key Concepts from 162A | |
| Jan 6 | Enzymes as Drug Targets | |
| Jan 8 | Enzymes: General Features | |
| Jan 11 | Enzymes: Principles of Catalysis | |
| Jan 15 | Enzymes: Mechanism and Kinetics | |
| Jan 22 | Enzyme Inhibition | |
| Jan 25 | Mechanism-Based Enzyme Inactivation | |
| Jan 29 | Structure-Based Drug Design: Intermolecular Interactions | |
| Feb 1 | Structure-Based Drug Design: Thermodynamics | |
| Feb 3 | Structure-Based Drug Design: Protein Structure Analysis | |
| Feb 8-10 | Structure-Based Drug Design: Docking | |
| Feb 17 | Structure-Based Drug Design: Modeling Protein Flexibility | Feb 24-26 | Pharmacokinetics and ADMET Challenges |
| March 1 | Drug Metabolism: Principles | |
| March 3 | Drug Metabolism: Overview | |
| March 3 | Drug Metabolism: P450 | |
| March 5 | P450 Pharmacogenetics, Drug Toxicity & Interactions | |
| Mar 8 | Prodrugs and Drug Delivery |
| Literature | Required reading in PDF | Acrobat |
| Enzymes | Transition State Binding | |
| Enzymes | Enzymatic Transition State Theory | |
| Enzymes | Protein Kinase Inhibitors | |
| SBDD | The Process of Structure-Based Drug Design | |
| SBDD | The Many Roles of Computation in Drug Discovery | |
| SBDD | Protein-ligand docking: Current Status and Future Challanges | |
| SBDD | High-throughput docking | |
| SBDD | High-throughput docking: thyroid hormone receptor | |
| Prodrugs | Lessons Learned from Marketed and Investigational Prodrugs | |
| Drug Delivery | Targeted Nanoparticles for Cancer Therapy |
Suggested literature can be found on a separate page
The assignments are posted one week before the due date. Answers shall be submitted electronically no later than the midnight of the due date.
| Assignments | PDF files | Acrobat |
| 1 | Modeling of Chemical Reactions | Link |
| 2 | Visualization of Macromolecules | Link |
| 3 | Molecular Interactions | Link |
| 4 | Design of Covalent Inhibitors | Link |
| 5 | Structure-based Drug Design: Docking | Link |
| 6 | Drug Metabolism and Prodrugs |
The assignment keys are typically posted one week after the due date.
| Keys | PDF files | Acrobat |
| 1 | Chorismate Mutase Transition State | Link |
| 3 | Molecular Interactions: Model Systems | Link |
| 4 | Covalent Inhibitors | |
| 5 | Molecular Interactions: Docking | Link |
| 6 | Drug Metabolism |
The project milestone guides are typically posted week and a half before they are due.
| Project Info | General Guidelines to Project Development |
Students in this course encounter many terms which have specific meaning in the context of drug design and medicine. You may find our glossary helpful when reading some of the assigned papers. If you encounter a term that is not in this dictionary, you could try a specialized medicinal chemistry glossary at www.chem.qmw.ac.uk/iupac/medchem ,an on-line dictionary at www.dictionary.com or an on-line encyclopedia at www.wikipedia.com . Feel free to send any additions and suggestions to Kalju Kahn
PyMOL Home Page
Biomolecular Images for Teaching with PyMOL
SYBYL Tutorial
Short List of Programs
Modern Drug Discovery
Nature Reviews Drug Discovery
Drug Discovery and Development
Drug Design Lecture Notes by Dr. Hugo Kubinyi
Oxford Drug Resistance Group Lectures
Basic Pharmacokinetics
Calcium Channel Blockers
Brain Chemistry
Acetylcholine Receptor
Dr. Andrew Boa lecture notes
An Overview of Marine Drug Discovery
Electronic Journals at UCSB
Google Web Search Engine
Biology Workbench
ExPASy Molecular Biology Server
Protein Data Bank
Periodic Table of the Elements
Cell and Molecular Biology Protocols Online
UCSB General Catalog
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