Drug Design Flashcards
What is the key role the neuraminidase enzyme plays for influenza?
Why is it important for us to know?
Without this enzyme, new viruses are no longer able to bud from the host cells.
Single subunit of influenza virus looks like:
Note, there are 4 of these in the whole enzyme.
6-bladed propeller.
Why is this sugar important?
A very common neruaminic acid.
Important because this is one of the VERY common sugars on human cell surfaces that neuraminidase (influenza virus enzyme) cleaves to gain access into host.
What is the proposed reaction for neuraminidase catalyzed glycoside hydrolysis reaction.
Orange square is where Neruaminidase stabilizes reaction.
What do you need to know about DANA?
A transition state analog neruaminidase inhibitor.
Pros: would inhibit neruaminidase
Cons: poor affinity (requires high concentration of drug), also affects human neuraminidase.
Note: planarity!
Scientists changed DANA to take out the partially negative charged hydroxyl group because it was next to Glu (neg. Amino acid) and replace it with a positively charged side group.
It helped significantly!
Remember for Ki: smaller values = stronger inhibition.
So strengthen binding for Flu Neruaminidase and weaken binding to human neuraminidase.
For orally available medicines a fine balances required. What are the two things that it needs to balance?
