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Responsive hybrid block co-polymer conjugates of proteins-controlled architecture to modulate substrate specificity and solution behaviour

Yasayan, Gökçen, Saeed, Aram O., Fernández-Trillo, Francisco, Allen, Stephanie, Davies, Martyn C., Jangher, Abdulhakim, Paul, Alison ORCID:, Thurecht, Kristofer J., King, Stephen M., Schweins, Ralf, Griffiths, Peter Charles, Magnusson, Johannes P. and Alexander, Cameron 2011. Responsive hybrid block co-polymer conjugates of proteins-controlled architecture to modulate substrate specificity and solution behaviour. Polymer Chemistry 2 (7) , pp. 1567-1578. 10.1039/c1py00128k

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Responsive co-polymers based on polyethyleneglycol methacrylate (PEGMA) monomers have been grown by aqueous phase ATRP from a model protein, trypsin, to generate hybrid polymer-protein block conjugates. The conjugates (Hybrids I and II) both contained the same segment of grafted responsive co-polymer to afford a phase transition at 37 °C, Hybrid II however differed from Hybrid I by having a second block of hydrophilic pPEGMA monomer grown from the end of the responsive block. The resultant ‘diblock’ and ‘triblock’ hybrids were characterised in terms of their temperature-dependent behaviour in solution by dynamic light scattering, small-angle neutron scattering and pulsed-gradient spin-echo NMR, and their structures at surfaces examined by aqueous phase atomic force microscopy and cryo transmission electron microscopy. These data showed that Hybrids I and II differed in their solution behaviour with temperature, dependent on the arrangement of their grafted polymer blocks. Hybrid I self-assembled into higher-order structures above 37 °C before precipitating reversibly, whereas Hybrid II remained essentially constant in size across a similar temperature range even when its attached intermediate polymer block underwent a phase transition. The differences in polymer-protein hybrid behaviour were also manifest in enzyme activity assays with temperature-dependent hydrolysis of both peptide and protein substrates varying with hybrid architecture. Overall the data show that it is possible to grow responsive polymer-protein block co-polymers of varied structures, architectures and solution behaviour and that these can be used to control bioconjugate activity

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Subjects: Q Science > QD Chemistry
Publisher: Royal Society of Chemistry
ISSN: 1759-9954
Last Modified: 18 Oct 2022 12:23

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