Building linear polymers from monomers

Scientists in the Netherlands have confirmed that supramolecular polymerisation occurs via ring-chain polymerisation, establishing a design for linear polymers based on monomer chains.

Researchers at the University of Technology in Eindhoven linked together a peptide and a protein using a flexible oligo(ethylene glycol) linker. The peptide and the protein end groups can bind reversibly to form an active enzyme complex but the complexes can form either between the two linked ends of one of these monomers or between multiple monomers, forming either linear or cyclic supramolecules. 

The paper is the first article to be published in the Royal Society of Chemistry's new flagship journal Chemical Science.

Bert Meijer, who led the team of researchers, said: "Our work used the most novel techniques in chemical biology to modify proteins in the making of hybrid systems and uses the knowledge of polymer chemistry to interpret these novel supramolecular structures with dynamic interchange. The fact that the linking unit is an enzyme makes the characterisation unique as well as that structures are made that have different physical properties at different concentrations."

The scientists examined how linker length affects the type of product formed. As the self-assembled supramolecular architectures increase in weight and size with every additional monomer, the group was able to separate them using size exclusion chromatography, which they coupled to a mass spectrometer so they could work out how much of each supramolecule there was. 

Combining this with theoretical modelling, they were able to confirm that supramolecular polymerisation occurs via ring-chain polymerisation or, in other words, the linear polymers are in equilibrium with their cyclic counterparts and the cyclic monomer is always formed in the greatest amount over other cyclic oligomers.  Anyone who wants linear polymers can therefore follow the design requirements for the monomers set out in this paper.

Whereas the linking together of molecular fragments is a common approach in chemical biology, the effect of linker length, structure and rigidity on the binding affinities of the construct is seldom studied. This paper describes the quantitative analysis of the self-assembly of peptide and protein fragments linked via a flexible oligo(ethylene glycol) linker that, upon complexation, form an active enzyme complex.

Because of the tethering of the peptide and protein fragment, the system is able to reversibly polymerize into linear oligomers which are in equilibrium with their corresponding cyclic counterparts. To study the effect of linker length and the resulting changes in effective concentration, two systems were synthesised that varied in the number of ethylene oxide units in the linker, resulting in different effective concentrations.

By combining experimental data with theoretical modelling, valuable insights were obtained into the supramolecular polymerization mechanisms and design criteria for protein based supramolecular polymeric architectures.

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