Guarise Cristian, Shinde Sandip, Kibler Karen, Ghirlanda Giovanna, Prins Leonard J, Scrimin Paolo
University of Padova, Department of Chemical Sciences, via Marzolo 1, 35131 Padova, Italy.
Arizona State University, Department of Chemistry and Biochemistry, PO Box 871604, Tempe, AZ 85287-1604, USA.
Tetrahedron. 2012 Jun 10;68(23):4346-4352. doi: 10.1016/j.tet.2012.03.078. Epub 2012 Apr 7.
The peptide sequence AcNH-TEG-Glu-Aib-Trp-AibAib-Trp-AibAib-Ile-Asp-OH (), designed to display the WWI epitope found near the C-terminus of gp41, an envelope glycoprotein decorating the surface of the HIV-1 virus, has been synthesized and proved to have a relevant content of helical conformation because of the presence of five α-aminoisobutyric acid (Aib) units. Three copies of it have been connected to a tripodal platform based on 2,4,6-triethylbenzene-1,3,5-trimethylamine. The tripodal template is even more structured than thus suggesting a significant interaction between the three sequences connected to the platform. Preliminary inhibition assays of HIV-mediated cell fusion indicated that while the single peptide is inactive within the concentration range of our assay, when it is conjugated to the tripodal platform, it is moderately active. These promising results suggest that our approach constitute a valid alternative to those reported so far.
肽序列AcNH-TEG-Glu-Aib-Trp-AibAib-Trp-AibAib-Ile-Asp-OH（），其设计用于展示在gp41 C末端附近发现的WWI表位，gp41是一种装饰HIV-1病毒表面的包膜糖蛋白，已被合成，并由于存在五个α-氨基异丁酸（Aib）单元而被证明具有相关含量的螺旋构象。它的三个拷贝已连接到基于2,4,6-三乙苯-1,3,5-三甲胺的三脚架平台上。三脚架模板比其结构更紧密，这表明连接到平台的三个序列之间存在显著相互作用。HIV介导的细胞融合的初步抑制试验表明，虽然单个肽在我们的测定浓度范围内无活性，但当它与三脚架平台缀合时，它具有中等活性。这些有希望的结果表明，我们的方法是迄今为止报道的方法的有效替代方案。
