MS/MS Sequencing of Digitally Encoded Poly(alkoxyamine amide)s

Abstract

International audienceMonodisperse sequence-coded oligo(alkoxyamine amide)s were thoroughly investigated by tandem mass spectrometry to evaluate the robustness of this analytical approach as a reliable sequencing methodology. Studied samples were synthesized by orthogonal iterative chemistry on a solid support, and the 0/1 coding system was based on the mass of two amide synthons that alternate with a nitroxide moiety. The major fragmentation pathway experienced by these co-oligomers proceeded via homolysis of all fragile C-ON bonds between a coding unit and a nitroxide moiety. The relative rate of competing C-ON bond cleavages was observed to be sequence-dependent, offering an additional means to validate the sequences reconstructed from the MS/MS fragments. The same fragmentation rules applied for all studied samples, varying in terms of chain length, charge state, encoded sequence, end-groups, and nitroxide moiety. Ion mobility separation was coupled to MS/MS to sequence some more complex co-oligomers composed of both different nitroxides and coding units

Coding and decoding libraries of sequence-defined functional copolymers synthesized via photoligation

“…As a consequence, most reports rarely describe a variation of the sequence order and/or the incorporated functionalities to generate highly diverse libraries of sequence-defined macromolecules and subsequently exploit this diversity to decode the coded chemical information52. Herein, we demonstrate how highly efficient photochemical reactions combined with a simple macromolecular design concept can lead to functional sequence-defined linear macromolecules.…”

Recent Progress in the Design of Monodisperse, Sequence-Defined Macromolecules

“…Furthermore, the approach was investigated on a soluble polymer support, which enabled the synthesis of even longer oligomer chains (compare Section ). The fragmentation behavior of the obtained macromolecules was studied in detail using MS/MS techniques in the positive and in the negative mode . In both modes, the fragmentation behavior followed the same pathway: the labile CON bonds dissociate and the thereof obtained fragments can be analyzed .…”

“…The fragmentation behavior of the obtained macromolecules was studied in detail using MS/MS techniques in the positive and in the negative mode . In both modes, the fragmentation behavior followed the same pathway: the labile CON bonds dissociate and the thereof obtained fragments can be analyzed . The required anhydride compound, 2‐bromopropionic anhydride, was synthesized in one step starting from 2‐bromopropionic acid .…”

Tandem mass spectrometry sequencing in the negative ion mode to read binary information encoded in sequence‐defined poly(alkoxyamine amide)s

“…As recommended by Wesdemiotis et al for the nomenclature of synthetic polymer product ions, these main product ions were named c i •+ when holding the α termination (a carboxymethyl moiety) or y i •+ when containing the bromine ω end‐group (Supplementary Scheme S1, Supporting Information). This fragmentation behavior was observed regardless of the size, charge state and coded sequence of the dissociating oligomer . Because coding moieties could be readily distinguished based on their 14 Da mass difference, the complete sequence coverage offered by MS/MS allowed any oligomers to be decoded in a straightforward and robust manner.…”