Mass spectrometry sequencing of long digital polymers facilitated by programmed inter-byte fragmentation

Abdelaziz Al Ouahabi (1) , Jean-Arthur Amalian (2) , Laurence Charles (2) , Jean-Francois Lutz (1)

1 ICS - Institut Charles Sadron
2 ICR - Institut de Chimie Radicalaire

In the context of data storage miniaturization, it was recently shown that digital information can be stored in the monomer sequences of non-natural macromolecules. However, the sequencing of such digital polymers is currently limited to short chains. Here, we report that intact multi-byte digital polymers can be sequenced in a moderate resolution mass spectrometer and that full sequence coverage can be attained without requiring pre-analysis digestion or the help of sequence databases. In order to do so, the polymers are designed to undergo controlled fragmentations in collision-induced dissociation conditions. Each byte of the sequence is labeled by an identification tag and a weak alkoxyamine group is placed between 2 bytes. As a consequence of this design, the NO-C bonds break first upon collisional activation, thus leading to a pattern of mass tag-shifted intact bytes. Afterwards, each byte is individually sequenced in pseudo-MS3 conditions and the whole sequence is found.Digital information can be stored in monomer sequences of non-natural macromolecules, but only short chains can be read. Here the authors show long multi-byte digital polymers sequenced in a moderate resolution mass spectrometer. Full sequence coverage can be attained without pre-analysis digestion or the help from sequence databases.

Mots clés: oligonucleotides; macromolecules; information-storage; phosphoramidite; robust; chemistry; defined polymers; dna; efficient

Domaines: Chimie

Abdelaziz Al Ouahabi, Jean-Arthur Amalian, Laurence Charles, Jean-Francois Lutz. Mass spectrometry sequencing of long digital polymers facilitated by programmed inter-byte fragmentation. Nature Communications, 2017, 8 (1), pp.967. ⟨10.1038/s41467-017-01104-3⟩. ⟨hal-01774259⟩