Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, FI-00014 University of Helsinki, Helsinki, Finland.
Curr Med Chem. 2014 Apr;21(10):1247-54. doi: 10.2174/0929867320666131119125045.
Low molecular weight oligonucleotides have been discovered to have potential use for gene therapy by selectively inhibiting the expression of certain genes. Chemical conjugation of functional peptides to oligonucleotides can introduce desired properties to the oligonucleotides, such as cell-specific delivery, cellular uptake efficiency, and/or intracellular distribution. In this paper, targeting peptides are conjugated to antisense interleukin-6 via a copper (I) catalyzed alkyne-azide cycloaddition click reaction. A simple and reproducible solution-phase conjugation procedure was investigated. Oligonucleotide-peptide conjugations were characterized by reverse-phase high-pressure liquid chromatography and mass spectrometry. The results show that the targeting peptides can be used for targeting delivery of oligonucleotides using the aforementioned conjugation.
现已发现，通过选择性抑制某些基因的表达，低分子量寡核苷酸在基因治疗方面具有潜在的应用价值。将功能性肽化学偶联到寡核苷酸上可以为寡核苷酸引入所需的性质，如细胞特异性递药、细胞摄取效率和/或细胞内分布。在本文中，通过铜（I）催化的叠氮-炔烃环加成点击反应将靶向肽与反义白细胞介素-6 偶联。研究了一种简单且可重现的溶液相偶联程序。通过反相高压液相色谱和质谱对寡核苷酸-肽缀合物进行了表征。结果表明，上述偶联可用于靶向递送寡核苷酸的靶向肽。
