Open AccessSpiro Diorthoester (SpiDo), a Human Plasma Stable Acid-Sensitive Cleavable Linker for Lysosomal Release
Author(s) -
Geoffray Leriche,
Marc Nothisen,
Nadège Baumlin,
Christian D. Muller,
Dominique Bagnard,
Jean-Serge Rémy,
Sylvain A. Jacques,
Alain Wagner
Publication year - 2015
Publication title -
bioconjugate chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.279
H-Index - 172
eISSN - 1520-4812
pISSN - 1043-1802
DOI - 10.1021/acs.bioconjchem.5b00280
Subject(s) - chemistry , linker , hydrolysis , förster resonance energy transfer , human plasma , combinatorial chemistry , high performance liquid chromatography , chromatography , biochemistry , fluorescence , physics , quantum mechanics , computer science , operating system
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.
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