Spiro Di-orthoester (SpiDo), a Human Plasma Stable Acid-Sensitive Cleavable Linker for Lysosomal Release.

Fiche publication


Date publication

juillet 2015

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BAGNARD Dominique, Dr MULLER Christian, Dr WAGNER Alain


Tous les auteurs :
Leriche G, Nothisen M, Baumlin N, Muller CD, Bagnard D, Remy JS, Jacques SA, Wagner A

Résumé

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 demonstrated to be good candidate for such linkers. Following an HPLC screen, a Spiro Di-orthoester (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 a high stability in Human plasma.

Référence

Bioconjug Chem. 2015 Jul 1.