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Muramyl dipeptide bound to poly-l-lysine substituted with mannose and gluconoyl residues as macrophage activators

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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.

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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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Authors and Affiliations

  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

    Danièle Derrien, Patrick Midoux, Claire Petit, Eric Nègre, Roger Mayer, Michel Monsigny & Annie-Claude Roche

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  1. Danièle Derrien
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  2. Patrick Midoux
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  3. Claire Petit
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  4. Eric Nègre
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  5. Roger Mayer
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  6. Michel Monsigny
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  7. Annie-Claude Roche
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Derrien, D., Midoux, P., Petit, C. et al. Muramyl dipeptide bound to poly-l-lysine substituted with mannose and gluconoyl residues as macrophage activators. Glycoconjugate J 6, 241–255 (1989). https://doi.org/10.1007/BF01050652

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  • DOI: https://doi.org/10.1007/BF01050652

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