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


Yasayan G. , Saeed A. O. , Fernandez-Trillo F., Allen S., Davies M. C. , Jangher A., ...More

POLYMER CHEMISTRY, vol.2, no.7, pp.1567-1578, 2011 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 2 Issue: 7
  • Publication Date: 2011
  • Doi Number: 10.1039/c1py00128k
  • Title of Journal : POLYMER CHEMISTRY
  • Page Numbers: pp.1567-1578

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 degrees 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 degrees 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.