Kida Shinya, Maeda Mitsuko, Hojo Keiko, Eto Yusuke, Gao Jian-Qing, Kurachi Shinnosuke, Mizuguchi Hiroyuki, Hayakawa Takao, Mayumi Tadanori, Nakagawa Shinsaku, Kawasaki Koichi
Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Nishi-ku, Kobe 651-2180, Japan.
Bioorg Med Chem Lett. 2006 Feb;16(3):743-5. doi: 10.1016/j.bmcl.2005.08.116. Epub 2005 Dec 6.
A Tat-related peptide, acetyl-Gly-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-Pro-Pro-Gln-Gly-Cys amide, designed to transport an Adenovirus vector (Ad) into cells, was synthesized. The synthetic peptide was conjugated to Ad, which potentially can act as an efficient carrier of heterologous genes into cells. The Tat-related peptide was synthesized using the solid phase method and then was coupled to the heterofunctional cross-linking reagent, 6-maleimidohexanoic acid N-hydroxysuccinimide ester. The resulting peptide-succinimidohexanoic acid N-hydroxysuccinimide ester was conjugated to Ad containing the luciferase gene. B16BL6 cells infected with the peptide-conjugated Ad luciferase gene construct exhibit a 50-fold greater luciferase activity than B16BL6 cells infected with wild-type Ad containing the luciferase gene.
合成了一种与Tat相关的肽,即乙酰基-甘氨酸-精氨酸-精氨酸-精氨酸-精氨酸-精氨酸-谷氨酰胺-精氨酸-精氨酸-精氨酸-脯氨酸-脯氨酸-谷氨酰胺-甘氨酸-半胱氨酸酰胺,其设计目的是将腺病毒载体(Ad)转运到细胞中。将合成肽与Ad偶联,Ad有可能作为异源基因进入细胞的有效载体。采用固相法合成与Tat相关的肽,然后将其与异功能交联剂N-羟基琥珀酰亚胺基6-马来酰亚胺己酸偶联。所得的肽-N-羟基琥珀酰亚胺基己酸与含有荧光素酶基因的Ad偶联。用肽偶联的Ad荧光素酶基因构建体感染的B16BL6细胞比用含有荧光素酶基因的野生型Ad感染的B16BL6细胞表现出高50倍的荧光素酶活性。