肝靶向配体半乳糖基白蛋白和多聚谷氨酸

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

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（ＧａｌｎＨＳＡ）和半乳糖基多聚Ｌ谷氨酸（ＧａｌｎＰＬＧＡ），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．

Two kinds of artificial ligand of asialoglycoprotein receptor (ASGPR), galactosyl human serum albumin (Gal n HSA) and galactosyl poly L glutamic acid (Gal n PLGA), were synthesized chemically. IC 50 of synthetic ligands inhibiting the binding of 125 I asialofetuin ( 125 I ASF) to ASGPR of rat liver cell membrane were assayed. The results showed that Gal 12 HSA, Gal 15 HSA, Gal 26 HSA, Gal 30 HSA and Gal 34 PLGA could all efficiently inhibit the binding of 125 I ASF to ASGPR. The affinities of Gal n HSA increased along with the increase of the coupling number of galactosyl. Here, the synthesis and the affinity identification of Gal 34 PLGA 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.