Cornell University Background
Macromolecules such as DNA, RNA, proteins, can be described as sequence-controlled biopolymers composed of monomer sequences of different chemical nature that are organized in specific ordered patterns. Various synthetic methods have been identified however none have achieved the complexity and regularity similar to macromolecules in nature. It still remains challenging to develop synthetic polymers containing controlled monomer sequences, which are stable, scalable, and allow structural diversity.
Cornell researchers have investigated a novel support-mediated synthesis allowing a sequential polymer assembly that is rapid, precise and functional.
This method () uses allyl acrylamide monomer with dithiol attached to a removable fluorous tag support. The latter, in addition to the orthogonal thiol-Michael and thiol-ene addition reactions are advantageous because they enable rapid solution kinetics at room temperature and pressure. Further, monomer addition is performed in solution and polymer purification is on a supported solid phase. The process allows for the synthesis of a 5-mer macromolecule (5 allyl acrylamide units and 5 dithiols) in a few hours.
M. Porel & C. A. Alabi. (2014). Sequence-Defined Polymers via Orthogonal Allyl Acrylamide Building Blocks. J.Am. Chem. Soc., 136 (38):13162–13165
Stage of Development
Proof of concept: 14 allyl acrylamide monomers have been designed and synthetized thus far. Using allylacrylamide monomers and dithiol co-monomers, 5-mer to 16-mer polymers have been synthetized to date though larger polymers can also be made. Additional experiments, using a red blood cell (RBC) hemolysis assay, demonstrated that the synthesized polymers can be designed to be hemolytic and thus could be used as endosomolytic agents.
Rapid reaction kinetics that allow faster polymer assembly: 5 – 30 min per monomer cycle
Efficient method compared to solid phase synthetic approach
Higher coupling yield
Facile synthesis of allyl acrylamide monomers
Method for controlling spatial assembly of allyl acrylamide monomers
Synthetic macromolecules with controlled properties (functional, macroscopic, etc.)
Synthetic polymers for drug delivery
Synthetic polymers for antibacterial activity
Synthesis of compounds for surface coating
Synthetic polymers for high throughput screening assay
Library of synthetic polymers