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

Yaşayan, Gökçen, Saeed, Aram O. ORCID: https://orcid.org/0000-0003-2903-5875, Fernández-trillo, Francisco, Allen, Stephanie, Davies, Martyn C., Jangher, Abdulhakim, Paul, Alison, Thurecht, Kristofer J., King, Stephen M., Schweins, Ralf, Griffiths, Peter C., 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. ISSN 1759-9954

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Abstract

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
Faculty \ School:	Faculty of Science > School of Pharmacy (former - to 2024)
UEA Research Groups:	Faculty of Science > Research Groups > Drug Delivery and Pharmaceutical Materials (former - to 2017) Faculty of Science > Research Groups > Pharmaceutical Materials and Soft Matter
Depositing User:	Pure Connector
Date Deposited:	22 Oct 2013 21:20
Last Modified:	24 Sep 2024 10:42
URI:	https://ueaeprints.uea.ac.uk/id/eprint/43816
DOI:	10.1039/c1py00128k

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