Uses of Protein Structure in Molecular Medicine Flashcards
What are the two methods used to deduce protein structure?
NMR and X-ray crystallography
What are pharmacokinetic properties?
solubility , membrane permeability, biological lifetime.
Describe structure assisted drug design.
Structure here is not being used for de novo drug sythesis. We are using established interactions and then building off of that to alter pharmacokinetic properties, improve binding, increase specificity, combat drug resistance, stabilize vaccines.
The ligand protein interaction has to be hand in glove rather than key in lock because the protein has to be dynamic. We have to analyze the conformations.
What is the lead compound
You took potential drugs then did a random screening against your specific target protein. You find the ones that interact the way you want and that is your lead compound. From there you analyze the ligand-protein complex for interactions and see how you can change the properties and improve your drug.
Dipeptidyl Peptidase-4
DPP-IV inhibitors
what does it treat? How does it work?
DPP - is DiaBETES 2
RHYMES YO.
DPP-IV gives you diabetes 2
The inhibitors will prevent small peptide hormones from small intenstine (GLP-1, GIP) from being degraded.
GLP-1, GIP decreases the level of fasting glucose in the blood.
Causes and Consequence of Diabetes
Causes: the muscle takes up and uses less glucose
- the pancreas has defective insulin hormone which takes glucose to be stored as glycogen in the liver. Insulin is the hormone that balances your glucose levels. It will bind to glucose if there is excess and bring it to liver. Or it will release glucose if blood sugar is low.
- the liver is producing glucose
Consequences: heart disease, stroke, vision loss, kidney failure
What are the effects of GLP-1 and GIP
- decrease gastric emptying so you feel full
- decrease glucagon secretion (released by the pancreas which converts glycogen to glucose)
- decreased food intake.
