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Precise Alkoxyamine Design to Enable Automated Tandem Mass Spectrometry Sequencing of Digital Poly(phosphodiester)s
Author(s) -
Launay Kévin,
Amalian JeanArthur,
Laurent Eline,
Oswald Laurence,
Al Ouahabi Abdelaziz,
Burel Alexandre,
Dufour Florent,
Carapito Christine,
Clément JeanLouis,
Lutz JeanFrançois,
Charles Laurence,
Gigmes Didier
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202010171
Subject(s) - phosphodiester bond , tandem mass spectrometry , side chain , chemistry , electron transfer dissociation , combinatorial chemistry , mass spectrometry , computer science , polymer , chromatography , biochemistry , organic chemistry , rna , gene
A major step towards reliable reading of information coded in the sequence of long poly(phosphodiester)s was previously achieved by introducing an alkoxyamine spacer between information sub‐segments. However, MS/MS decoding had to be performed manually to safely identify useful fragments of low abundance compared to side‐products from the amide‐based alkoxyamine used. Here, alternative alkoxyamines were designed to prevent side‐reactions and enable automated MS/MS sequencing. Different styryl‐TEMPO spacers were prepared to increase radical delocalization and stiffness of the structure. Their dissociation behavior was investigated by EPR and best results were obtained with spacers containing in‐chain benzyl ring, with no side‐reaction during synthesis or sequencing. Automated decoding of these polymers was performed using the MS‐DECODER software, which interprets fragmentation data recorded for each sub‐segment and re‐align them in their original order based on location tags.