Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
32 Cards in this Set
- Front
- Back
|
Exam #2 begins with Lecture 11. What is the title of Lecture 11, and what is it about? |
Drug Development.
This lecture is about how different drugs react with the different components of our bodies, what makes a good drug, specific types of drugs that have special characteristics, etc. |
|
|
There are two main processes that can lead to the discovery of a drug. What are they? |
A) Compound--> Physiological effect ---> Molecular target
B) Molecular target--> Compound ---> Physiological effect |
|
|
What are 3 major challenges that drug developers face? |
1) Drug candidates must be potent modulators of their targets 2) Drugs must have suitable properties to reach their targets 3) Drugs that are too toxic will harm the person. |
|
|
What is one way to measure/test whether or not the drug will bind to the target very strongly? |
Check the dissociation constant (Kd) to estimate the affinity between the two molecules. |
|
|
Is a drug that has a low Kd good or bad? |
If you have a low Kd that means the drug is very good because you only need a small amount of the drug to bind to the receptor of the target so you want it to have a very high affinity and very low Kd. |
|
|
What does EC mean? |
Effective concentrations. |
|
|
What does ADME mean? |
Absorbed Distributed Metabolism Excreted
|
|
|
List Lipinkski's 3 Rules about the absorption of drugs. |
1) The molecular weight must be below 500. 2) The molecular cannot be too polar meaning that it has more than 10 H-Bond acceptors, and more than 5 H-Bond donors. 3) The molecule cannot be very hydrophobic or it will get stuck in the middle of the phospholipid bilayer. (Very hydrophobic if the partition coefficient is greater than 5) |
|
|
What does the paritition coefficient measure? |
Paritition coefficient means to measure the tendency of a molecule to dissolve in the membrane |
|
|
Why is morphine an ideal drug? |
Morphine has molecule weight of 285 2 H-bond donors 4 H-bond acceptors log(P)=1.27 |
|
|
What are the two main terms used to describe the pathway the body uses to remove drugs when it thinks the drugs are a bad foreign substance? |
Oxidation and Conjugation |
|
|
What happens during oxidation? |
Uses cytochrome P450 enzyme in the liver which recognizes the drug and adds a hydroxyl group. Makes the drug more soluble therefore easier to excrete. |
|
|
What happens during conjugation? |
glutathione (be able to recognize the structure) has three amino acids. 1 is glutamic acid, cystine, and glycine (KNOW HOW TO RECOGNIZE GLYCINE)
Kind of confused about what conjugation is still. |
|
|
Why can too much tylenol lead to liver failure? |
Too much tylenol can lead to liver failure because the cyto p450 oxidizes the acetaminophen in the tylenol which then depletes the gutathione in the liver
35% of all liver failures in the U.S. is due to an overdose of tylenol |
|
|
What protein serves as the main carrier for hydrophobic drugs in the bloodstream? |
Albumin |
|
|
What were two main drugs that were serendipitous observations? |
Penicillin and Sildenafil |
|
|
What is Sildenafil also known as today? |
Viagra |
|
|
What is cGMP? |
A very important signaling molecule in the cell. |
|
|
What does the inhibition of the enzyme cGMP lead to? |
Muscle relaxation |
|
|
How does aspirin work? |
Aspirin blocks arachidonate to prostaglandin which leads to pain -aspirin binds to the active site of prostaglandin transfer the acetyl group to the side chain becomes covalently modified irreversible inhibitor - aspirin |
|
|
What is the most effective drug against malaria right now? |
Artemisinin |
|
|
What are the 3 phases to test a future drug? |
phase 1= 5-10 people test the safety of the drug to see if they die or not.
phase 2=checks safety efficacy dosage which tests which or not the drug actually kills the problem. given to patients the drug may actually benefit as a test.
Phase 3= safety efficacy given to the larger population checks any potential side effects
Then it is put into a clinical use. |
|
|
Sildenafil is a potent inhibitor of what? |
Phosphodiesterase 5
|
|
|
What are the most he most versatile macromolecules in living systems and serve crucial functions in essentially all bio processes? |
Proteins |
|
|
What are the three ways a protein can bind to another protein? |
-surface string (one protein forms a surface with a crease and the other one forms a loop and the loop fits into the crease) KINANSE/SUBSTRATE-example
-Helix to helix one protein forms a helix and another protein forms a helix and the two wrap around each other to forma a coil-coil structure. GENE REGULATORY PROTEINS- example It is IMPORTANT to know what promotes coil to coil structure. I don’t think he gives a direct answer so LOOK IT UP.
-Surface-surface (most common way) Both proteins have matching surface. Polarity and shape compliment each other. Very strong if a lot of non covalent interactions are formed. Then the Kd would be very low |
|
|
What are two ways to identify the interacting proteins for a protein of interesest? |
-affinity purification followed by mass spectrometry identification
-yeast two-hybrid screen |
|
|
What it focuses on the movement of ions in the vacuum in the electric/magnetic field to identify proteins? |
Mass spectrometry |
|
|
Speed of this is precisely determined by what? |
Mass/Charge |
|
|
ESI and SLD (Discovered by John B. Fenn and Koichi Tanaka) will allow the protein molecule to become ionized and enter the gas phase.
True or false. |
True |
|
|
What does FRET stand for? |
Fluorescence Resonance Energy Transfer (FRET)- energy transfer will only happen in the donor and acceptor are extremely close |
|
|
How does FRET and Jellyfish help us when learning about proteins? |
Able to detect proteins interactions by using the colors lights to check how close two molecules are close together in the cells. Measures the distance between two proteins. |
|
|
What technique allows identification of binding partners of a protein of interest? |
affinity purification followed by mass spectrometry
|
