A Targeted Peptide Nucleic Acid To Down-Regulate Mouse Microsomal Triglyceride Transfer Protein Expression in Hepatocytes
作者： Sabine M. W. van Rossenberg , Karen M. Sliedregt-Bol , Perry Prince , Theo J. C. van Berkel , Jacques H. van Boom
DOI: 10.1021/BC0340417
关键词:
摘要: Peptide nucleic acids (PNA's) have shown to hold potential as antisense drugs. In this study we designed PNA drugs for the microsomal triglyceride transfer protein (MTP), which is known play a critical role in assembly of atherogenic lipoproteins, and converted most potent drug into liver-targeted prodrug. First, synthesized three sequences targeting domains on mouse MTP mRNA, were not involved intrastrand base-pairing interactions jugded from its secondary structure. Only one PNA's, PNA569, showed dose-dependent inhibition expression cell-free system coupled transcription/translation MTP. Second, improve cellular uptake drug, conjugated PNA569 high affinity ligand asialoglycoprotein receptor, K(GalNAc)2. As compared parent PNA, prodrug PNA−K(GalNAc)2 was found display markedly improved capacity inhibit mRNA parenchymal liver cells. A glycoconjugated ...
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