Synthesis of Monodisperse Sequence-Coded Polymers with Chain Lengths above DP100

Abstract

International audienceNon-natural, sequence-encoded polyphosphates were prepared using the phosphoramidite approach on a DNA synthesizer. Two phosphoramidite monomers, namely, 2-cyanoethyl (3-dimethoxytrityloxy-propyl) diisopropylphosphoramidite (0) and 2-cyanoethyl (3-dimethoxytrityloxy-2,2-dimethyl-propyl) diisopropylphosphoramidite (1), were used in this approach to form binary-coded sequences. Using 1000 A controlled pore glass as a support and a large excess of monomers at each step, it was possible to synthesize homopolymers and sequence-coded copolymers of high chain-length. For instance, monodisperse polymers containing 16, 24, 56, and 104 coded monomer units were synthesized and characterized in this work. These results indicate that highly efficient phosphoramidite steps are suitable for the synthesis of long non-natural information-containing macromolecules

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

“…Several read‐out strategies, such as tandem MS, NMR as well as depolymerization methods were proposed and discussed in a recently published minireview . In the approach described above, the solid‐phase synthesis was conducted manually, whereas in another approach a non‐natural polyphosphate with a DP above 100 was synthesized by using two different monomers in a conventional DNA synthesizer . To do so, the synthesis protocol from Beaucage and Carothers was applied, but non‐natural phosphoramidites served as monomers .…”

Convenient Graphical Visualization of Messages Encoded in Sequence‐Defined Synthetic Polymers Using Kendrick Mass Defect Analysis of their MS/MS Data

“…As a consequence of this synthesis pathway, each repeat unit of the digital polymer contains both a phosphodiester and an alkoxyamine linkage. PAPs should, however, not be confused with digital polyphosphodiesters containing inter‐byte alkoxyamine linkages, which are prepared via a relatively different chemical approach . For example, in the PAP type I (PAP‐I) shown in inset of Figure a, coding is based on the alkyl segment (between the amide and phosphodiester) holding R = H for the 0 ‐bit or R = CH 3 for the 1 ‐bit.…”

Self‐Assembly of Multiblock Copolymers

“…Monodisperse polymers and BCPs would allow addressing fundamental questions related to polymer physics, but also shine light of its effect on size dispersity of superstructures (a correlation is to be expected). Optimized polymerization conditions already reach near‐monodisperse weight distributions, while other methods build polymers monomer by monomer . It remains to be seen what and how strong the effect of exact block lengths will be.…”