Synthesis of Non-Natural Sequence-Encoded Polymers Using Phosphoramidite Chemistry

Abstract

Sequence-defined non-natural polyphosphates were prepared using iterative phosphoramidite protocols on a polystyrene solid support. Three monomers were used in this work: 2-cyanoethyl (3-dimethoxytrityloxy-propyl) diisopropylphosphoramidite (0), 2-cyanoethyl (3-dimethoxytrityloxy-2,2-dimethyl-propyl) diisopropylphosphoramidite (1), and 2-cyanoethyl (3-dimethoxytrityloxy-2,2-dipropargyl-propyl) diisopropylphosphoramidite (1'). Phosphoramidite coupling steps allowed rapid synthesis of homopolymers and copolymers. In particular, the comonomers (0, 1), (0, 1'), and (1, 1') were used to synthesize sequence-encoded copolymers. It was found that long encoded sequences could be easily built using phosphoramidite chemistry. ESI-HRMS, MALDI-HRMS, NMR, and size exclusion chromatography analyses indicated the formation of monodisperse polymers with controlled comonomer sequences. The polymers obtained with the comonomers (0, 1') and (1, 1') were also modified by copper-catalyzed azide-alkyne cycloaddition with a model azide compound, namely 11-azido-3,6,9-trioxaundecan-1-amine. (1)H and (13)C NMR analysis evidenced quantitative modification of the alkyne side-chains of the monodisperse copolymers. Thus, the molecular structure of the coding monomer units can be easily varied after polymerization. Altogether, the present results open up interesting avenues for the design of information-containing macromolecules.

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

“…Directly inspired by biologically accessible DNA systems—for example, nucleobase-coded chains—sequence-defined macromolecules have been synthesized employing template-based coding strategies26272829 or via the generation of regulated sequence alternating thymine hybrid polymers30, as well as the design of reactions with iterative protection/deprotection steps on supports3132. Further, bulk reactions have been conducted in flow systems based on iterative synthesis33.…”

Coding Macromolecules: Inputting Information in Polymers Using Monomer-Based Alphabets

“…73 We have shown in a recent publication that phosphoramidite chemistry also allows convenient synthesis of non-natural sequence-coded polyphosphates. 74 Non-nucleoside phosphoramidite monomers were studied in this work ( Figure 2a). In order to implement a code in the polymer chains, two phosphoramidite monomers containing a propyl and a 2,2-dimethylpropyl synthon were used as 0 and 1 bit, respectively.…”

Silica Mineralization of DNA‐Inspired 1D and 2D Supramolecular Polymers

“…In our previous studies, we developed several systems capable of mimicking various aspects of nucleic acids . For this purpose, we took advantage of the supramolecular polymerization of short aromatic oligophosphates . These self‐assembled structures appear as one‐ or two‐dimensional objects sharing common structural features—a hydrophobic core of aromatic chromophores shielded from the aqueous environment by a network of negatively charged phosphates .…”