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Synthesis of dendritic polyglycerol anions and their efficiency toward L-selectin inhibition

M. Weinhart, D. Gröger, S. Enders, J. Dernedde, R. Haag – 2011

A versatile route for the synthesis of highly functionalized, polyanionic macromolecules based on dendritic polyglycerol was applied by means of the Huisgen–Sharpless–Meldal 1,3-dipolar cycloaddition (“click-reaction”) of polyglycerolazide precursors and alkyne-functionalized anions such as sulfonates, carboxylates, phosphonates, and bisphosphonates. In addition, the corresponding polyglycerol phosphate has been synthesized via direct hydroxyl interconversion of polyglycerol to the corresponding phosphate with a degree of functionalization >80% by analogy to the synthesis of previously reported polyglycerol sulfates (dPGS). On the basis of the finding that dPGS exhibits high affinity for L- and P-selectin, the potential of these novel polyanionic, multivalent macromolecules of varying anionic nature as L-selectin inhibitors has been evaluated in vitro by means of a competitive concentration dependent binding assay. Affinity of all polyanions toward L-selectin was demonstrated with distinct IC50 values ranging from the low nanomolar to the high micromolar range. The efficiency of L-selectin inhibition increases in the order carboxylate < phosphate < phosphonate ≈ sulfonate < bisphosphonate < sulfate. Additional DLS and ζ-potential measurements of these polyanions were performed to correlate their binding affinity toward L-selectin with their anionic nature. However, a direct correlation of effective charge and particle size with the determined IC50 values turned out to require further in-depth studies on the microstructure of the polyanions but clearly indicate an exceptional position of dPGS among the studied dendritic polyelectrolytes.

Titel
Synthesis of dendritic polyglycerol anions and their efficiency toward L-selectin inhibition
Verfasser
M. Weinhart, D. Gröger, S. Enders, J. Dernedde, R. Haag
Datum
2011
Kennung
10.1021/bm200250f
Zitierweise
Biomacromolecules 2011, 12, 2502-2511
Art
Text
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