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Synthesis of Dendritic Polyglycerol Anions and Their Efficiency Toward L-Selectin Inhibition

Marie Weinhart, Dominic Gröger, Sven Enders, Jens Dernedde, Rainer 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.

Title
Synthesis of Dendritic Polyglycerol Anions and Their Efficiency Toward L-Selectin Inhibition
Author
Marie Weinhart, Dominic Gröger, Sven Enders, Jens Dernedde, Rainer Haag
Publisher
ACS
Date
2011-05-20
Identifier
DOI: 10.1021/bm200250f
Citation
Biomacromolecules, 2011, 12 (7), 2502–2511.
Language
eng
Type
Text