Bodé Catherine A, Bechet Tom, Prodhomme Emmanuel, Gheysen Katelijne, Gregoir Pieter, Martins José C, Muller Claude P, Madder Annemieke
Laboratory for Organic and Biomimetic Chemistry, Department of Organic Chemistry, Ghent University, B-9000 Gent, Belgium.
Org Biomol Chem. 2009 Sep 7;7(17):3391-9. doi: 10.1039/b907395g. Epub 2009 Jul 7.
The current article reports the design, synthesis and biochemical evaluation of a cyclic bile acid-peptide conjugate as a mimic of the loop-like structure of the measles virus haemagglutinin noose epitope (HNE). This macrocyclic structure was assembled by solid phase synthesis. Scaffold-peptide ring closure was achieved via the introduction of a succinate linker. After disulfide bridge formation with iodine, the desired 14 amino acid cyclic conjugate was obtained with overall yields between 15 and 35%. NMR analysis supports the presence of a helical conformation in the Q384-G388 pentapeptide portion, in agreement with the organisation of this chain in the native protein. The compound was found to have increased biostability compared to stabilised linear peptides, displayed good binding towards monoclonal antibodies known to bind to HNE and thus has potential in an alternative peptide-based measles vaccine.
本文报道了一种环状胆汁酸-肽共轭物的设计、合成及生化评估，该共轭物可模拟麻疹病毒血凝素套索表位（HNE）的环状结构。这种大环结构通过固相合成组装而成。通过引入琥珀酸连接子实现支架肽的环化。在用碘形成二硫键后，得到了所需的14氨基酸环状共轭物，总产率在15%至35%之间。核磁共振分析支持在Q384 - G388五肽部分存在螺旋构象，这与该链在天然蛋白中的结构一致。与稳定的线性肽相比，该化合物具有更高的生物稳定性，对已知能结合HNE的单克隆抗体表现出良好的结合能力，因此在基于肽的替代麻疹疫苗中具有潜力。
