Interesting prodrug bioconverting enzyme paper out!

Hard work pays off! We have finalized one very interesting and also very important project, in which we were able to identify our L-type amino acid transporter 1 (LAT1)- utilizing prodrugs bioconverting enzyme from mouse brain. This was aminopeptidase B and it requires cobalt and slightly basic (ca. pH 8) conditions to be active and break down the amide bonds that we have in some of our prodrugs. We have long overlooked the amide prodrugs bioconverting enzymes, since we haven't had the right conditions in our in vitro studies to see any bioconversion, but we have seen the release of the active parent drugs in vivo and particularly in the mouse brain, so we have been confident that there is an enzyme for our prodrugs. Curiously, aminopeptidase B was more abundant in the brain than in plasma and liver, making it superior enzyme for brain-targeted purposes. In addition, we identified a bunch other good enzyme candidates for prodrugging and targeting prodrugs in the brain by global proteomic approach. 

The project itself was also a long one, I think we started it in autumn 2017 and many ERASMUS students were participating to this one. Therefore, I'm deeply thankful for all co-authors for their hard work and also everyone who has supported the study. The results were published in a special issue (Prodrug Design and Therapeutic Applications) of the journal called Frontiers in Pharmacology under a title "Aminopeptidase B can bioconvert L-type amino acid transporter 1 (LAT1)-utilizing amide prodrugs in the brain (link to the publication)".

And most importantly, the main conclusion of this stud was is that now we can design even better prodrugs bioconverted selectively by aminopeptidase B in the brain, in future.