In this research we describe the improvement of the water‐solubility of cyclic epitope mimics based on the HCV E2 glycoprotein by incorporation of suitable polar hinges. The poor solubility of epitope mimics based on peptide sequences in the envelope (E2) protein hampered their synthesis and purification and made it very difficult to prepare the molecular constructs for evaluation of their bioactivity. Since changes in the amino acid composition are hardly possible in these epitope mimics in order to increase water‐solubility, a polar cyclization hinge may offer a remedy leading to a significant increase of polarity and therefore water solubility. These polar hinges were applied in the synthesis of better water‐soluble HCV‐E2 epitopes. An azide functionality in the polar hinges allowed attachment of a tetraethylene glycol linker by Cu‐catalyzed azide‐alkyne cyclo‐addition (CuAAC) for a convenient conjugation to ELISA plates in order to evaluate the bio‐activity of the epitope mimics. The immunoassays showed that the use of more polar cyclization hinges still supported anti‐HCV antibody recognition and did not negatively influence their binding. This significantly increased solubility induced by polar hinges should therefore allow for the molecular construction and ultimate evaluation of synthetic vaccine molecules.

中文翻译：

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使用 POLAR 铰链环化提高 HCV-E2 糖蛋白表位模拟物的水溶性。

在这项研究中，我们描述了通过掺入合适的极性铰链来改善基于 HCV E2 糖蛋白的环状表位模拟物的水溶性。基于包膜（E2）蛋白中的肽序列的表位模拟物的溶解度差阻碍了它们的合成和纯化，并且使得制备用于评估其生物活性的分子构建体变得非常困难。由于在这些表位模拟物中几乎不可能改变氨基酸组成以增加水溶性，因此极性环化铰链可能提供一种补救措施，导致极性显着增加，从而显着增加水溶性。这些极性铰链被应用于合成更好的水溶性 HCV-E2 表位。极性铰链中的叠氮官能团允许通过铜催化叠氮炔环加成 (CuAAC) 连接四乙二醇接头，以便方便地与 ELISA 板缀合，以评估表位模拟物的生物活性。免疫测定表明，使用极性更强的环化铰链仍然支持抗 HCV 抗体识别，并且不会对其结合产生负面影响。因此，由极性铰链引起的溶解度显着增加应该允许合成疫苗分子的分子构建和最终评估。