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Updated: Mar 28, 2026

Synthesis and Mass Spectrometry Analysis of Oligo-peptoids
Published on: February 21, 2018
Tandem mass spectrometry sequencing in the negative ion mode to read binary information encoded in sequence-defined
Laurence Charles1, Chloé Laure2, Jean-François Lutz2
1Aix-Marseille Université - CNRS, UMR 7273, Institut de Chimie Radicalaire, Marseille Cedex 20, France.
Rationale:
Digitally encoded oligomers composed of two distinct amide coding units spaced by a nitroxide moiety were recently decrypted using a tandem mass spectrometry (MS/MS) sequencing approach developed for protonated oligomers. Here, the MS/MS behavior of deprotonated oligomers was explored in the negative ion mode to provide both structural and mechanistic complementary information.
Methods:
Binary-encoded oligo(alkoxyamine)amides, containing coding 0/1 amide units spaced by a TEMPO nitroxide moiety, were ionized in negative ion mode electrospray thanks to their α end-group containing a carboxylic acid function. Deprotonated molecules were subjected to collision-induced dissociation in MS/MS and MS(3) experiments, combined with accurate mass measurements, for a thorough investigation of their dissociation behavior.
Results:
Deprotonated oligomers readily dissociated upon collisional activation via competitive homolytic cleavages of all fragile alkoxyamine linkages between any coding 0 or 1 monomers and a nitroxide moiety. As expected, only product ions holding the deprotonated α end-group were detected while complementary moieties containing the ω termination were released as radicals. The so-formed distonic radical anions were observed to further depolymerize according to a radical-induced process, as evidenced by MS(3) experiments.
Conclusions:
Messages encoded in oligo(alkoxyamine)amides were readily decrypted by MS/MS sequencing performed in the negative ion mode. When compared with results obtained in positive ion mode ESI-MS/MS, these data provided further evidence regarding the influence of adducted proton on the charge-remote homolytic cleavage of alkoxyamine linkages.
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