Click and Clear
We investigated the opportunity offered by bioorthogonal chemistry for in vivo drug neutralization. We designed a small-molecule anticoagulant drug containing an azide group (WN3) that acts as a safety pin allowing drug deactivation via in vivo click reaction with a suitable cyclooctyne-based neutralizing agent (BCN-peg6-OH). The new molecule formed by reaction of the drug and the antidote was shown to be deprived of biological activity and prone to fast renal clearance.
Among all mechanisms of biological processes regulation, control of acidity plays the most prominent role. Proton transfer is the most frequent reaction that enzymes perform. General acid and general base catalysis are first-line for the making and breaking of covalent bonds that define the chemistry of metabolic processes.
In addition, acidic extracellular pH misregulation is a major feature of tumor tissue.
Also, lysosomes are other example of ubiquitous biological mechanism inherently linked to tight acidification control.
Reflecting on this recognition that acido-basic reactions are the fundament of life, at BFC we investigate how exogenous chemical systems can make use or mimic these well controlled biological mechanisms to develop novel delivery systems and catalysts for in vivo synthesis.