Site-Directed Conjugation of "Clicked" Glycopolymers To Form Glycoprotein Mimics: Binding to Mammalian Lectin and Induction of Immunological Function
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- 作者：Jin Geng ; Giuseppe Mantovani ; Lei Tao ; Julien Nicolas ; Gaojian Chen ; Russell Wallis ; Daniel A. Mitchell ; Benjamin R. G. Johnson ; Stephen D. Evans ; David M. Haddleton
- 刊名：Journal of the American Chemical Society
- 出版年：2007
- 出版时间：December 12, 2007
- 年：2007
- 卷：129
- 期：49
- 页码：15156 - 15163
- 全文大小：384K
- 年卷期：v.129,no.49(December 12, 2007)
- ISSN：1520-5126
文摘
Synthesis of well-defined neoglycopolymer-protein biohybrid materials and a preliminary studyfocused on their ability of binding mammalian lectins and inducing immunological function is reported. Crucialintermediates for their preparation are well-defined maleimide-terminated neoglycopolymers (Mn = 8-30kDa; Mw/Mn = 1.20-1.28) presenting multiple copies of mannose epitope units, obtained by combinationof 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 resultingbioconjugates 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 thiswork was demonstrated by preparing a small library of conjugating glycopolymers that only differ fromeach other for their relative epitope density were prepared by coclicking of appropriate mixtures ofmannopyranoside and galactopyranoside azides to the same polyalkyne scaffold intermediate. Surfaceplasmon resonance binding studies carried out using recombinant rat mannose-binding lectin (MBL) showedclear and dose-dependent MBL binding to glycopolymer-conjugated BSA. In addition, enzyme-linkedimmunosorbent assay (ELISA) revealed that the neoglycopolymer-protein materials described in this workpossess significantly enhanced capacity to activate complement via the lectin pathway when comparedwith native unmodified BSA.