5: Protein Conjugate Therapies

This entry intends to be a review of different therapies that use proteins as drugs.

Reversible Pegylation Prolongs the Hypotensive Effect of Atrial Natriuretic Peptide
Nesher, et al. 2008 Bioconjug Chem 19 342-348.

Signficance
I only skimmed this one, but natriuresis (doctors out there) is the excretion of sodium in urine, a physiological response that promotes hypotension and gets rid of excess sodium. This is triggered by endogenous brain and atrial natriuretic peptide.
They wanted to make these peptides stick around longer, to combat things like hypertension, so they reversibly attached a lot of PEG to the end of it.

Criticism
The result? They have a drug that sticks around longer, but it's only 10% as effective as the real thing. They did radiolabelled ligand competition experiments to analyze binding to the receptor, then just looked at the compound sitting in buffer to analyze the rate of hydrolysis (apparently this is similar to looking at it degrade in human serum? I don't really believe that one...). Finally, they administered the prodrug to mice and watched their blood pressure go down.