Muramyl dipeptide bound to poly-l-lysine substituted with mannose and gluconoyl residues as macrophage activators |
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Authors: | Danièle Derrien Patrick Midoux Claire Petit Eric Nègre Roger Mayer Michel Monsigny Annie-Claude Roche |
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Institution: | (1) Départment de Biochimie des Glycoconjugués et Lectines Endogènes, Centre de Biophysique Moléculaire, CNRS, INSERM et Université d'Orléans, 1 rue Haute, 45071 Orléans Cedex 02, France |
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Abstract: | Poly-l-lysine modified with mannose derivatives, the residual cationic charges of which being neutralized byN-acylation, were synthesized and used as carriers of a macrophage activator (N-acetylmuramyl dipeptide, MDP). The influence of the acylating agent on the targeting efficiency was investigated: a hydrosolubilizing group such as a gluconoyl moiety led to very efficient carrier conjugates, while an acetyl group did not. The effect of sugar and acyl content of the polymers was assessed using these compounds as inhibitors of red blood cell agglutination by Concanavalin A. The binding and specific endocytosis of poly-l-lysine substituted with several mannose derivatives and gluconoyl residues (GlcAx-, Many-PLK) have been determined by a quantitative flow cytometry analysis. MDP bound to these conjugates was much more efficientin vitro than free MDP in macrophage cytostasis assays.Abbreviations MDP
N-acetylmuramyl dipeptide
- PLK
poly-l-lysine
- BSA
bovine serum albumin
- BOC
t-butyloxycarbonyl
- DMF
dimethylformamide
- DCHU
N, N -dicyclohexylurea
- DCCl
N, N -dicyclohexylcarbodiimide
- TEA
triethylamine
- Su
succinimidyl
- DMSO
dimethylsulfoxide
- FITC
fluoresceinyl isothiocyanate
- RPMI
Roswell Park Memorial Institute
- PBS
phosphate buffered saline
- Fl
fluoresceinyl
- GG
glycyl-glycyl |
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Keywords: | drug carrier targeting macrophage membrane lectin endocytosis macrophage activation |
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