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Sequence‐Defined Oligomers from Hydroxyproline Building Blocks for Parallel Synthesis Applications
Author(s) -
Kanasty Rosemary L.,
Vegas Arturo J.,
Ceo Luke M.,
Maier Martin,
Charisse Klaus,
Nair Jayaprakash K.,
Langer Robert,
Anderson Daniel G.
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201602748
Subject(s) - biomolecule , monomer , sequence (biology) , polymer , conjugated system , combinatorial chemistry , hydroxyproline , solid phase synthesis , nanotechnology , chemistry , materials science , organic chemistry , peptide , biochemistry
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. We developed a controlled synthesis of novel oligomers from hydroxyproline‐based building blocks and conjugated these materials to siRNA. Hydroxyproline‐based monomers enable the incorporation of broad structural diversity into defined polymer chains. Using a perfluorocarbon purification handle, we were able to purify diverse oligomers through a single solid‐phase extraction method. The efficiency of synthesis was demonstrated by building 14 unique trimers and 4 hexamers from 6 diverse building blocks. We then adapted this method to the parallel synthesis of hundreds of materials in 96‐well plates. This strategy provides a platform for the screening of libraries of modified biomolecules.