Sequence-Defined Oligomers via Hydroxyproline Building Blocks for Parallel Synthesis Applications

Abstract

The functionality of natural biopolymers has inspired significant effort to develop sequence-defined synthetic polymers for applications including molecular recognition, self-assembly, and catalysis. Conjugation of synthetic materials to biomacromolecules has played an increasingly important role in drug delivery and biomaterials. Here we develop the controlled synthesis of novel oligomers from hydroxyproline-based building blocks and conjugate these materials to siRNA. Hydroxyproline-based monomers enable incorporation of broad structural diversity into defined polymer chains. Using a perfluorocarbon purification handle, we are able to purify diverse oligomers with a single solid phase extraction method. We show the efficiency of synthesis by building 14 unique trimers and 4 hexamers from 6 diverse building blocks. We adapt this method to parallel synthesis of hundreds of materials in 96-well plates. This strategy provides a platform for library screening of modified biomolecules.