肝靶向配体半乳糖基白蛋白和多聚谷氨酸

化学合成两类去唾液酸糖蛋白受体(ASGPR)的人工配体——半乳糖基白蛋白(Gal_nHSA)和半乳糖基多聚-L-谷氨酸(Gal_nPLGA), 并以 ¹²⁵I标记的去唾液酸胎球蛋白(ASF)为标准配体，测定了合成配体抑制 ¹²⁵I-ASF与大鼠肝细胞膜ASGPR结合的IC₅₀值. 结果表明，Gal₁₂HSA、Gal₁₅HSA、Gal₂₆HSA、Gal₃₀HSA和Gal₃₄PLGA均能够有效地抑制 ¹²⁵I-ASF与ASGPR的结合，且前者与ASGPR的亲和力随半乳糖基化程度的增加而增加. 这些合成配体来源丰富、制备简单，适合于作为药物或基因肝靶向运送的导向配体.

Liver Targeting Ligands:Galactosyl Albumin and Galactosyl Poly-L-glutamic Acid

Two kinds of artificial ligand of asialoglycoprotein receptor (ASGPR), galactosyl human serum albumin (Gal_nHSA) and galactosyl poly-L-glutamic acid (Gal_nPLGA), were synthesized chemically. IC₅₀ of synthetic ligands inhibiting the binding of ¹²⁵I-asialofetuin (¹²⁵I-ASF) to ASGPR of rat liver cell membrane were assayed. The results showed that Gal₁₂HSA, Gal₁₅HSA, Gal₂₆HSA, Gal₃₀HSA and Gal₃₄-PLGA could all efficiently inhibit the binding of ¹²⁵I-ASF to ASGPR. The affinities of Gal_nHSA increased along with the increase of the coupling number of galactosyl. Here, the synthesis and the affinity identification of Gal₃₄PLGA with ASGPR were firstly reported. These synthetic ligands with abundant sources and simple preparations may be used as targeting ligands for the liver-targeting delivery of drugs or genes.