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Site-directed conjugation of "Clicked" glycopolymers to form glycoprotein mimics: Binding to mammalian lectin and induction of immunological function

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Geng, Jin, Mantovani, Giuseppe, Tao, Lei, Nicolas, Julien, Chen, Gaojian, Wallis, Russell, Mitchell, Daniel Anthony, Johnson, Benjamin R. G., Evans, Stephen D. and Haddleton, David M.. (2007) Site-directed conjugation of "Clicked" glycopolymers to form glycoprotein mimics: Binding to mammalian lectin and induction of immunological function. Journal of the American Chemical Society, Vol.129 (No.49). pp. 15156-15163. ISSN 0002-7863

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Official URL: http://dx.doi.org/10.1021/ja072999x

Abstract

Synthesis of well-defined neoglycopolymer-protein biohybrid materials and a preliminary study focused on their ability of binding mammalian lectins and inducing immunological function is reported. Crucial intermediates for their preparation are well-defined maleimide-terminated neoglycopolymers (M-n = 8-30 kDa; M-w/M-n = 1.20-1.28) presenting multiple copies of mannose epitope units, obtained by combination of transition-metal-mediated living radical polymerization (TMM LRP) and Huisgen [2+3] cycloaddition. Bovine serum albumin (BSA) was employed as single thiol-containing model protein, and the resulting bioconjugates were purified following two independent protocols and characterized by circular dichroism (CD) spectroscopy, SDS PAGE, and SEC HPLC. The versatility of the synthetic strategy presented in this work was demonstrated by preparing a small library of conjugating glycopolymers that only differ from each other for their relative epitope density were prepared by coclicking of appropriate mixtures of mannopyranoside and galactopyranoside azides to the same polyalkyne scaffold intermediate. Surface plasmon resonance binding studies carried out using recombinant rat mannose-binding lectin (MBL) showed clear and dose-dependent MBL binding to glycopolymer-conjugated BSA. In addition, enzyme-linked immunosorbent assay (ELISA) revealed that the neoglycopolymer-protein materials described in this work possess significantly enhanced capacity to activate complement via the lectin pathway when compared with native unmodified BSA.

Item Type: Journal Article
Subjects: Q Science > QD Chemistry
Divisions: Faculty of Science > Chemistry
Faculty of Medicine > Warwick Medical School > Clinical Sciences Research Institute (CSRI)
Journal or Publication Title: Journal of the American Chemical Society
Publisher: American Chemical Society
ISSN: 0002-7863
Date: 12 December 2007
Volume: Vol.129
Number: No.49
Number of Pages: 8
Page Range: pp. 15156-15163
Identification Number: 10.1021/ja072999x
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
URI: http://wrap.warwick.ac.uk/id/eprint/30882

Data sourced from Thomson Reuters' Web of Knowledge

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