University:
The University Of Western Ontario
Course:
Biology 2290F | Scientific Method in Biology
Academic year:

2024
Views:

31

Pages:

3
Author:

Kyuwon J.

HIV proposal ● Allosteric inhibitors -Binds to non-active sites and inturuptes overall structure/and binding affinity Key receptors ● Gp120-HIV receptor will bind to CD4 of host ● Gp41- allowed fusion on membrane allowing viral genome to enter the host ● CD4- host cell receptor that binds to Gp120 of HIV. Lupinski’s rule of 5 1. MW<500 Da 2. Drug< 5HBD 3. Drug <10 HBA 4. CLogP<5 Gp120 allosteric inhibitors ● GP120 a receptor on exterior of HIV membrane is used to interact with host receptor CD4. ● When create an allosteric inhibitor, gp120 would not bind to CD4 in first place. ● As a cure for HIV, there still will be infected cells, however, in the fact that single HIV viridae’s average life span is short, inhibiting the potential to bind and replicate will see a cure in HIV. ● It is simple and easy to approach since its at the outside of the membrane. Therefore, our drug/inhibitors need to go through no, or minimal amount of membranes to bind ○ In drug design, the crossing membrane is crucial part, where it should follow lupinski’s rule of 5 very strictly ○ It must have distinct hydrophobic nature GP41 allosteric inhibitor ● GP41 could also be inhibited by allosteric inhibitors. ● This comes into play after the binding of CD4 and gp120 ○ It will go under conformational change where hydrophobic surface emerge. ● It is a sandwiched beta sheets, so if there were to be inhibitors that clogges into this sandwich and create a strong bond, such as sulfuric bond within the sandwich, will inhibit the conformational change of gp41 ● It is challenging to design this since it must go through several membranes. However, if we use High molecular weigh polar drug, it will cross over, using Pinocytosis. We would like to have it something like this, holding onto each sheets. CD4 inhibitions ● It is also possible, but it will lower the affinity to bind to other essential elements ● However, if its not permanent inhibitors(and most of allosteric is not) it would be overcome by increasing concentration of other elements.