title: Synthesis of dendritic polyglycerol anions and their efficiency toward L-selectin inhibition.
abstract: 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 IC(50) 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 IC(50) 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.
authors: Institute of Chemistry and Biochemistry, Freie Universitaet Berlin, Takustr. 3, 14195 Berlin, Germany.
authors: Marie
authors: M
authors: Weinhart
authors: Dominic
authors: D
authors: Gröger
authors: Sven
authors: S
authors: Enders
authors: Jens
authors: J
authors: Dernedde
authors: Rainer
authors: R
authors: Haag