BPS 2110 mid-term 1 2023 answers

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University of Ottawa *

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Biology

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Dec 6, 2023

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1 BPS 2110 Intro to Bio-Farm Mid Term 1 Answers 1. Various methods are used to discover leads in the drug industry. a. What are the five general types of lead identification methods used in drug discovery? ( 5 points ) High throughput screening Natural products Rational drug design De-novo design Combinatorial chemistry b. Which of the types in part a represent the three most commonly used methods used in the drug industry? ( 2 points ) High throughput screening Natural products Rational drug design c. List one advantage and one disadvantage for each of the methods you listed in part b. ( 6 points ) Some examples are provided. Many answers are possible. i. First method (HTS) Adv: Can be done quickly Has been proven to work (reliable), most drugs discovered this way Leads often have simple structures (easier to do SAR or manufacture) Leads may be exclusive to company (company database) Disadv: Generates lots of false positives Collections contain lots of PAINS Can take long time to eliminate false positives Structural variety limited (limited to what is in the collection) ii. Second method (Natural products) Adv: Has been proven to work (reliable) Natural compounds often very potent Often find new structures Can use local info to find them (poisons, local medicines) Can be available in large amounts (farmable, fermentable) Often have novel mechanisms of action (not otherwise obvious) Relies on academia (no cost to the company) May not need to optimize Company can market as “natural”
2 Disadv: Most of the “easy” ones have already been found (rate of discovery slower) Sometimes difficult to get large amounts Molecules may have complex structures (stereochemistry), difficult to make synthetic versions Limited by what nature gives you (may be hard to improve properties, modify structures) Searching by academia only (slower, public knowledge of lead) May not know mechanism of action iii. Third method (Rational drug design) Adv: Has been proven to work (reliable) Knowledge of structure and/or mechanism tend to speed up research Assays and other tools may already be available Design for simple structures Disadv: Requires knowledge of structure and/or mechanism Molecules may have complex structures (start with natural product) May require development of assays and other tools 2. Non-bonding interactions help to maintain protein structure and control drug binding. a. List the four types of non-bonding interactions in order from strongest to weakest ( 5 Points ) Electrostatics (ionic) Hydrogen bonding Dipole-dipole Van der Waals (London or dispersion) b. Describe two features of the strongest interaction type ( 2 Points ) Attraction between + and Strength depends on surrounding environment, stronger in non-polar environments Non-directional Strength depends on distance between charges c. Describe two features of the weakest interaction type ( 2 Points ) Attraction between induced dipoles created by electron circulation Strength depends on surface area (stronger with larger surfaces) Important in many binding pockets Non-polar environment improves the strength of the polar interactions Can improve potency of drugs by facilitating de-solvation Can improve potency of drugs by affecting equilibrium between free and bound drug
3 3. Use a diagram to describe: a) The way that a receptor molecule transfers information from one side of a membrane to another. ( 5 Points ) b) The way that an agonist works ( 3 Points ) Agonist binds to receptor. Receptor changes shape such that the normal signal is sent (shape change is normal ) c) The way that an inverse agonist works ( 5 Points ) Inverse agonist occurs when the receptor molecule produces a weak background signal (signal produced in absence of a messenger) Inverse agonist behaves like an antagonist, binding to the receptor and changing shape to prevent signal production. This has the effect of shutting off the background signal, producing a reduction in signal relative to a “normal” antagonist .
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