title: Natural and engineered kallikrein inhibitors: an emerging pharmacopoeia.
abstract: The kallikreins and kallikrein-related peptidases are serine proteases that control a plethora of developmental and homeostatic phenomena, ranging from semen liquefaction to skin desquamation and blood pressure. The diversity of roles played by kallikreins has stimulated considerable interest in these enzymes from the perspective of diagnostics and drug design. Kallikreins already have well-established credentials as targets for therapeutic intervention and there is increasing appreciation of their potential both as biomarkers and as targets for inhibitor design. Here, we explore the current status of naturally occurring kallikrein protease-inhibitor complexes and illustrate how this knowledge can interface with strategies for rational re-engineering of bioscaffolds and design of small-molecule inhibitors.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
authors.forename: Joakim E
authors.initials: JE
authors.lastname: Swedberg
authors.forename: Simon J
authors.initials: SJ
authors.lastname: de Veer
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Harris
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001682:Biological Availability; D001688:Biological Products / Q000493:pharmacokinetics / Q000494:pharmacology*; D004355:Drug Stability; D005818:Genetic Engineering; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D001688:Biological Products; D011480:Protease Inhibitors; D007610:Kallikreins