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Optimization of the Azobenzene Scaffold for Reductive Cleavage by Dithionite; Development of an Azobenzene Cleavable Linker for Proteomic Applications
Author(s) -
Leriche Geoffray,
Budin Ghyslain,
Brino Laurent,
Wagner Alain
Publication year - 2010
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201000546
Subject(s) - chemistry , linker , azobenzene , alkoxy group , benzoic acid , reactivity (psychology) , dithionite , combinatorial chemistry , alkyne , cleavage (geology) , alkyl , carboxylic acid , photochemistry , polymer chemistry , organic chemistry , polymer , catalysis , medicine , alternative medicine , enzyme , geotechnical engineering , pathology , fracture (geology) , computer science , engineering , operating system
In this paper we conducted an extensive reactivity study to determine the key structural features that favour the dithionite‐triggered reductive cleavage of the azo–arene group. Our stepwise investigation allowed identification of a highly reactive azo–arene structure 25 bearing a carboxylic acid at the ortho position of the electron‐poor arene and an ortho ‐ O ‐alkyl‐resorcinol as the electron‐rich arene. Based on this 2‐(2′‐alkoxy‐4′‐hydroxyphenylazo)benzoic acid (HAZA) scaffold, the orthogonally protected difunctional azo–arene cleavable linker 26 was designed and synthesized. Selective linker deprotection and derivatization was performed by introducing an alkyne reactive group and a biotin affinity tag. This optimized azo–arene cleavable linker led to a total cleavage in less than 10 s with only 1 m M dithionite. Similar results were obtained in biological media.