title: Chemical Tools for the Study of Intramembrane Proteases.
abstract: Intramembrane proteases (IMPs) reside inside lipid bilayers and perform peptide hydrolysis in transmembrane or juxtamembrane regions of their substrates. Many IMPs are involved in crucial regulatory pathways and human diseases, including Alzheimer's disease, Parkinson's disease, and diabetes. In the past, chemical tools have been instrumental in the study of soluble proteases, enabling biochemical and biomedical research in complex environments such as tissue lysates or living cells. However, IMPs place special challenges on probe design and applications, and progress has been much slower than for soluble proteases. In this review, we will give an overview of the available chemical tools for IMPs, including activity-based probes, affinity-based probes, and synthetic substrates. We will discuss how these have been used to increase our structural and functional understanding of this fascinating group of enzymes, and how they might be applied to address future questions and challenges.
authors.affiliation: Leibniz Institute for Analytical Sciences ISAS, e.V. , Otto-Hahn-Str. 6b, 44227 Dortmund, Germany.
authors.forename: Minh T N
authors.initials: MT
authors.lastname: Nguyen
authors.affiliation: Leibniz Institute for Analytical Sciences ISAS, e.V. , Otto-Hahn-Str. 6b, 44227 Dortmund, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Van Kersavond
authors.affiliation: Leibniz Institute for Analytical Sciences ISAS, e.V. , Otto-Hahn-Str. 6b, 44227 Dortmund, Germany.|KU Leuven - University of Leuven , Department of Cellular and Molecular Medicine, Laboratory of Chemical Biology, Herestr. 49 Box 802, 3000 Leuven, Belgium.
authors.forename: Steven H L
authors.initials: SH
authors.lastname: Verhelst
mesh_terms: D001665:Binding Sites; D002462:Cell Membrane / Q000737:chemistry / Q000201:enzymology*; D006801:Humans; D008958:Models, Molecular; D015335:Molecular Probes / Q000737:chemistry; D015394:Molecular Structure; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D011480:Protease Inhibitors
chemical_list: D015335:Molecular Probes; D011480:Protease Inhibitors; D010447:Peptide Hydrolases