Cutting back on pro-protein convertases: the latest approaches to pharmacological inhibition.
The secretory pathway in cells possesses an elaborate set of endoproteolytic enzymes that carry out a crucial step in protein precursor maturation. This step is proteolytic activation by cleavage at specific pairs of basic residues. These enzymes, named pro-protein convertases (PCs), are responsible for generating bioactive peptides and activating several enzymes and growth factors that are implicated in many important physiological events. PCs have roles in several pathologies including viral infections and cancers and, thus, are promising targets for therapeutic applications. Recent structural and homology-modeling studies demonstrate more similarity than expected at the catalytic site of the seven PCs, which makes the development of selective drugs to target individual PCs frustrating. Based on this information, we review the latest strategies to inhibit PCs, which might lead to the development of specific compounds.
Fugère
Martin
M
Institut de Pharmacologie de Sherbrooke, Département de Pharmacologie, Faculté de Médecine, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada.
Day
Robert
R
D000818:Animals; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000627:therapeutic use; D006801:Humans; D008958:Models, Molecular; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D015202:Protein Engineering
D004791:Enzyme Inhibitors; D043484:Proprotein Convertases