CELL-TYPE-SPECIFIC AND LIGAND SPECIFIC ENHANCEMENT OF CELLULAR UPTAKE OF OLIGODEOXYNUCLEOSIDE METHYLPHOSPHONATES COVALENTLY-LINKED WITH A NEOGLYCOPEPTIDE, YEE(AH-GALNAC)(3)

被引：59

作者：

HANGELAND, JJ ^{[1
]}

LEVIS, JT ^{[1
]}

LEE, YC ^{[1
]}

TSO, POP ^{[1
]}

机构：

[1] JOHNS HOPKINS UNIV, DEPT BIOL, BALTIMORE, MD 21218 USA

来源：

BIOCONJUGATE CHEMISTRY | 1995年 / 6卷 / 06期

关键词：

D O I：

10.1021/bc00036a006

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

A novel, structurally defined, and homogeneous oligodeoxynucleoside methylphosphonate (oligo-MP) neoglycopeptide conjugate, [YEE(ah-GalNAc)(3)]-SMCC-AET-pU(m)pT(7), has been synthesized. The linkage between the carbohydrate ligand and the oligo-MP is a metabolically stable thioether. Experiments establish that uptake of this conjugate by human hepatocellular carcinoma (Hep G2) is cell-type specific when compared with its uptake by human fibrosarcoma (HT 1080) and human promyleocytic leukemia (HL-60). Uptake of the conjugate with Hep G2 cells can be totally inhibited by the addition of a 100-fold excess of free YEE(ah-GalNAc)(3) in the culture medium indicating the observed cell uptake is ligand specific. The conjugate is rapidly taken in by Hep G2 cells in a linear fashion reaching a saturation plateau of 26 pmol per 10(6) cells after 24 h. Conjugation of oligo-MPs to ligands for hepatic carbohydrate receptors, such as YEE(ah-GalNAc)(3), represents an efficient and ligand-specific method for the intracellular delivery of oligo-MPs.

引用

页码：695 / 701

页数：7

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