title: Sequence-Defined Oligomers from 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. 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.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.|David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main St., Cambridge, MA, 02142, USA.
authors.forename: Rosemary L
authors.initials: RL
authors.lastname: Kanasty
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main St., Cambridge, MA, 02142, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, MA, 02115, USA.|Department of Chemistry, Boston University, 590 Commonwealth Avenue, Boston, MA, 02215, USA.
authors.forename: Arturo J
authors.initials: AJ
authors.lastname: Vegas
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main St., Cambridge, MA, 02142, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, MA, 02115, USA.|Department of Chemistry, Boston University, 590 Commonwealth Avenue, Boston, MA, 02215, USA.
authors.forename: Luke M
authors.initials: LM
authors.lastname: Ceo
authors.affiliation: Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Maier
authors.affiliation: Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA.
authors.forename: Klaus
authors.initials: K
authors.lastname: Charisse
authors.affiliation: Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA.
authors.forename: Jayaprakash K
authors.initials: JK
authors.lastname: Nair
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.|David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main St., Cambridge, MA, 02142, USA.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, MA, 02115, USA.|Division of Health Science Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.|Institute for Medical Engineering and Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.|Harvard-MIT Division of Health Science and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA. dgander@mit.edu.|David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main St., Cambridge, MA, 02142, USA. dgander@mit.edu.|Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, MA, 02115, USA. dgander@mit.edu.|Division of Health Science Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA. dgander@mit.edu.|Institute for Medical Engineering and Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA. dgander@mit.edu.|Harvard-MIT Division of Health Science and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA. dgander@mit.edu.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
mesh_terms: D006909:Hydroxyproline / Q000737:chemistry*; D015394:Molecular Structure; D011140:Polyurethanes / Q000138:chemical synthesis* / Q000737:chemistry; D052616:Solid Phase Extraction
chemical_list: D011140:Polyurethanes; D006909:Hydroxyproline
keywords: bioconjugates; fluorous synthesis; oligomers; sequence-defined polymers; siRNA