Blog Post 11
In this post, I’m kind of going to backtrack to one of the earlier steps. I mentioned earlier about testing whether the charge switching peptides are triggered by the enzyme. I forgot to talk about designing the structure of the peptide itself. That’s what the topic of this blog post is going to be. So, I designed the peptide structure using adobe illustrator. Essentially, the polyarginine peptide is basically a cell penetrating peptide that is also a peptide, meaning it consists of multiple peptides linked together. And a peptide consists of two or more amino acids linked together. In this case, the polyarginine is going to consist of several arginine groups, amine groups, and hydrogen bonds. I obtained the basic structure of the polyarginine and then I manipulated its structural properties to account for the charge-switch. Essentially, the ALP enzyme triggers the charge switch through a process called dephosphorylation. This is basically where the phosphate group is removed from a molecule and this is what causes the charge to increase from +1 to +3. You’ll notice that the structure on the left is RRRpY which is basically arginine arginine arginine phosphotyrosine and the structure on the right is RRRY, which is basically arginine arginine arginine tyrosine. Hence, we see the phospho prefix missing from tyrosine due to the phosphate group removal. So why do we need to charge switch in the first place? Well, nucleic acids aren’t able to pierce through the cell membrane due to their strong negative charge and they need something to effectively neutralize their charge. That’s where my creation of these charge-switching peptides comes in. The +1 charge is way too small in terms of an electrostatic force to effectively neutralize the negative charge. But, the positive +3 charge is strong enough to neutralize the negative charge of DNA and that way the peptide-DNA complex can effectively go into the cell and treat the cancer tumor. And remember, ALP triggers the peptide so that it can bind to the DNA and thus, this method is successful like I mention in the other blog posts.
