Institute for Research in Biomedicine (IRB Barcelona), Networking Center on Bioengineering, Biomaterials and Biomedicine (CIBER-BBN) and Institute for Advanced Chemistry of Catalonia (IQAC), Spanish Research Council (CSIC), Cluster Building, Baldiri Reixac 10, E-08028 Barcelona, Spain.
J Org Chem. 2010 Oct 15;75(20):6806-13. doi: 10.1021/jo101143j.
Novel lipid derivatives carrying amino and triazolyl groups were efficiently synthesized and covalently anchored at the 3'-termini of oligonucleotides. The desired amino-lipid conjugates were fully characterized by reversed-phase HPLC and MALDI-TOF mass spectrometry. The methodology was applied to the synthesis of lipid-siRNA designed to inhibit tumor necrosis factor (TNF-α) in order to obtain siRNAs with anti-inflammatory properties. The siRNA duplex carrying amino-lipids at the 3'-end of the passenger strand has inhibitory properties similar to those of unmodified RNA duplexes in HeLa cells, indicating that the new lipid derivatives are compatible with the RNA interference machinery.
新型带有氨基和三唑基的脂质衍生物被有效地合成，并共价连接到寡核苷酸的 3'-末端。期望的氨基脂质缀合物通过反相高效液相色谱法和 MALDI-TOF 质谱法进行了充分的表征。该方法应用于合成脂质-siRNA，旨在抑制肿瘤坏死因子 (TNF-α)，以获得具有抗炎特性的 siRNA。在带有氨基脂质的乘客链 3'-末端的 siRNA 双链体在 HeLa 细胞中具有与未修饰 RNA 双链体相似的抑制性质，表明新的脂质衍生物与 RNA 干扰机制相容。
