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

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• 作者：Marie Weinhart ; Dominic Gro虉ger ; Sven Enders ; Jens Dernedde ; Rainer Haag
• 刊名：Biomacromolecules
• 出版年：2011
• 出版时间：July 11, 2011
• 年：2011
• 卷：12
• 期：7
• 页码：2502-2511
• 全文大小：1055K
• 年卷期：v.12,no.7(July 11, 2011)
• ISSN：1526-4602

文摘

A versatile route for the synthesis of highly functionalized, polyanionic macromolecules based on dendritic polyglycerol was applied by means of the Huisgen鈥揝harpless鈥揗eldal 1,3-dipolar cycloaddition (鈥渃lick-reaction鈥? 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 鈮?sulfonate < bisphosphonate < sulfate. Additional DLS and 味-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.