Synthesis and Sequencing of Information-Containing Macromolecules – 00111001

The aim of the project 00111001 is to prepare synthetic information-containing macromolecules. Polymers containing sequence-coded information exist in Nature (e.g. DNA) but not in manmade materials. In the present project, digital information will be ‘written’ in synthetic polymers using two monomers defined as 0- and 1-bits. In particular, we will focus on the design of information-storing polymers that contain weak alkoxyamine bonds. Indeed, it was recently found by the applicants that the presence of alkoxyamine linkages in such polymers has important advantages: (i) it speeds-up and facilitates their synthesis, (ii) it greatly simplifies their sequencing by mass spectrometry, and (iii) it renders the formed polymers dynamic and allows potentially sequence manipulation. In this project, three synthetic routes will be considered for preparing alkoxyamine-containing polymers such as poly(alkoxyamine amide)s or poly(alkoxyamine phosphodiester)s. For each route, a wide variety of custom-made monomers will be screened. In particular, tailored nitroxides will be synthesized by the group of Didier Gigmes in Marseille. All polymers will be synthesized by the group of Jean-François Lutz in Strasbourg using iterative solid-phase chemistry. Moreover, automated protocols will be studied in order to prepare long sequence-coded polymers.

Another important target of the project will be to ‘read’ the sequences that are encrypted in the polymer chains. For that purpose, sequencing approaches, inspired by methodologies used in genomics and proteomics, will be studied. For instance, the sequences of the formed polymers will be analyzed by tandem mass spectrometry (MS/MS), MS3, and ion mobility spectrometry by Laurence Charles in Marseille but also by high field NMR by Marc-André Delsuc in Strasbourg. New sequencing tools like 2D-FTICR-MS will be also studied jointly by the groups of Delsuc and Charles. Before writing the present application, it was found that alkoxyamine-based sequence-encoded polymers are remarkably easy to sequence due to the presence of alkoxyamine weak links in their chains. For instance, these cleavable bonds enable an excellent “readability” in MS/MS sequencing. In the frame of the project, polymers containing different types of C-ON alkoxyamine bonds will be studied and sequenced. The objective will be to identify optimal structure/readability relationships. Some methods for erasing or scrambling sequence information will be also investigated. Indeed, alkoxyamine-containing polymers are thermolabile and therefore dynamic at elevated temperatures. In addition, photosensitive monomers will be designed. Thus, the digital information encrypted in the chains will be erased by heat or light. The rates and mechanisms of degradation will be studied in details. Overall, the project 00111001 should allow development of a new class of synthetic polymer materials that currently does not exist in manmade technologies.