Uses of Protein Structure in Molecular Medicine

Question 1

What are two methods to determine the three-dimensional structures of macromolecules?

Answer 1

X-ray crystallography and NMR spectroscopy

Question 2

Allows us to see rpotein connectivity (which atoms are next to which)

Answer 2

2D NMR

Question 3

Not used for de novo drug design

Answer 3

Structure

Question 4

What is the purpose of structure elucidation in drug design?

Answer 4

Help to redesign drugs to improve affinity, specificity, pharmodynamics, and toxicity

Question 5

The same forces that stabilize protein structure stabilize a ligands interaction with a

Answer 5

Protein

Question 6

Usually, drugs fail not because of the binding to the protein, but because of the

Answer 6

Pharmokinetics of the drug

Question 7

Removes an amino acid from GLP-1 and GIP, which inactivates the two metabolic hormones

Answer 7

DPP-4

Question 8

Inactivation of GLP-1 and GIP leads to

Answer 8

Overeating, furthering metabolic syndrome

Question 9

One attempt at treating type two diabetes was to

Answer 9

Inhibit DPP-4, thereby keeping GLP-1 and GIP active

Question 10

Lowers prandial and fasting glucose

Answer 10

GLP-1

Question 11

How did structural elucidation help in the attempt at synthesizing a nontoxic inhibitor of DPP-4?

Answer 11

Structural characterization of DPP-4 allowed for the inhibitors to be redesigned based on DPP-4’s structure

Question 12

Once two promising inhibitors were obtained, the important regions of these compounds were identified by knowing their structure. This then served as a scaffold for drug design to improve

Answer 12

Affinity, specificity, and pharmacokinetic properties