title: Spiro Diorthoester (SpiDo), a Human Plasma Stable Acid-Sensitive Cleavable Linker for Lysosomal Release.
abstract: pH-sensitive linkers designed to undergo selective hydrolysis at acidic pH compared to physiological pH can be used for selective release of therapeutics selectively at targets and orthoesters have been demonstrated to be good candidates for such linkers. Following an HPLC screening, a Spiro Diorthoester (SpiDo) derivative was identified as a potent acid-labile group for the development of pH-sensitive targeted systems. After incorporation of this linker into activatable FRET-based probe and side-by-side comparison to a well-known alkylhydrazone linker, this SpiDo linker has shown a fast and pH sensitive hydrolysis for mild acidic conditions, a pH sensitive lysosomal hydrolysis, and high stability in human plasma.
authors.forename: Geoffray
authors.initials: G
authors.lastname: Leriche
authors.forename: Marc
authors.initials: M
authors.lastname: Nothisen
authors.affiliation: §INSERM U1109 - MN3T Lab, University of Strasbourg, LabEx Medalis, Fédération de Médecine Translationnelle de Strasbourg (FMTS), 67000 Strasbourg, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Baumlin
authors.affiliation: ∥Laboratoire d'Innovation Thérapeutique, UMR 7200, CNRS University of Strasbourg, Faculty of Pharmacy, 74 route du Rhin, 67400 Illkirch, France.
authors.forename: Christian D
authors.initials: CD
authors.lastname: Muller
authors.affiliation: §INSERM U1109 - MN3T Lab, University of Strasbourg, LabEx Medalis, Fédération de Médecine Translationnelle de Strasbourg (FMTS), 67000 Strasbourg, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bagnard
authors.forename: Jean-Serge
authors.initials: JS
authors.lastname: Remy
authors.forename: Sylvain A
authors.initials: SA
authors.lastname: Jacques
authors.forename: Alain
authors.initials: A
authors.lastname: Wagner
mesh_terms: D000143:Acids / Q000737:chemistry*; D000818:Animals; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005453:Fluorescence; D006801:Humans; D006835:Hydrazones / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D008099:Liver / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D057054:Molecular Imaging; D010949:Plasma / Q000737:chemistry*
chemical_list: D000143:Acids; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D006835:Hydrazones