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Binding and Structural Properties of DNA Aptamers with VEGF-A-Mimic Activity
Molecular Therapy - Nucleic Acids ( IF 6.5 ) Pub Date : 2020-01-14 , DOI: 10.1016/j.omtn.2019.12.034 Toru Yoshitomi 1 , Misako Hayashi 1 , Takumi Oguro 1 , Keiko Kimura 1 , Fumiya Wayama 1 , Hitoshi Furusho 2 , Keitaro Yoshimoto 3
Molecular Therapy - Nucleic Acids ( IF 6.5 ) Pub Date : 2020-01-14 , DOI: 10.1016/j.omtn.2019.12.034 Toru Yoshitomi 1 , Misako Hayashi 1 , Takumi Oguro 1 , Keiko Kimura 1 , Fumiya Wayama 1 , Hitoshi Furusho 2 , Keitaro Yoshimoto 3
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Vascular endothelial growth factors (VEGFs) are hypoxia-inducible secreted proteins to promote angiogenesis, in which VEGF-A is an important molecule that binds and activates VEGF receptor-1 (VEGFR-1) and VEGFR-2. In this study, two DNA aptamers, Apt01 and Apt02, were successfully isolated by alternating consecutive systematic evolution of ligands by exponential enrichment (SELEX) against VEGFR-1 and -2 using deep sequencing analysis in an early selection round. Their binding affinities for VEGFR-2 were lower than that of VEGFR-1, which is similar to that of VEGF-A. Structural analyses with the measurements of circular dichroism spectra and ultraviolet melting curve showed that Apt01 possessed the stem-loop structure in the molecule, whereas Apt02 formed G-quadruplex structures. In addition, Apt02 accelerated a tube formation of human umbilical vein endothelial cells faster than Apt01, which was affected by difference of binding affinity and nuclease resistance due to G-quadruplex structures. These results demonstrated that Apt02 might have a potential to function as an alternative to VEGF-A.
中文翻译：
具有 VEGF-A-Mimic 活性的 DNA 适体的结合和结构特性
血管内皮生长因子（VEGF）是缺氧诱导的促进血管生成的分泌蛋白，其中VEGF-A是结合并激活VEGF受体-1（VEGFR-1）和VEGFR-2的重要分子。在本研究中，通过在早期选择轮中使用深度测序分析针对 VEGFR-1 和 -2 交替连续系统进化配体指数富集 (SELEX)，成功分离出两个 DNA 适体 Apt01 和 Apt02。它们对 VEGFR-2 的结合亲和力低于 VEGFR-1，与 VEGF-A 相似。圆二色光谱和紫外熔解曲线的结构分析表明，Apt01分子中具有茎环结构，而Apt02则形成G-四联体结构。此外，Apt02比Apt01更快地加速人脐静脉内皮细胞的管形成，这是由于G-四链体结构导致的结合亲和力和核酸酶抗性差异的影响。这些结果表明 Apt02 可能具有替代 VEGF-A 的潜力。
更新日期：2020-01-14
中文翻译：
具有 VEGF-A-Mimic 活性的 DNA 适体的结合和结构特性
血管内皮生长因子（VEGF）是缺氧诱导的促进血管生成的分泌蛋白，其中VEGF-A是结合并激活VEGF受体-1（VEGFR-1）和VEGFR-2的重要分子。在本研究中，通过在早期选择轮中使用深度测序分析针对 VEGFR-1 和 -2 交替连续系统进化配体指数富集 (SELEX)，成功分离出两个 DNA 适体 Apt01 和 Apt02。它们对 VEGFR-2 的结合亲和力低于 VEGFR-1，与 VEGF-A 相似。圆二色光谱和紫外熔解曲线的结构分析表明，Apt01分子中具有茎环结构，而Apt02则形成G-四联体结构。此外，Apt02比Apt01更快地加速人脐静脉内皮细胞的管形成，这是由于G-四链体结构导致的结合亲和力和核酸酶抗性差异的影响。这些结果表明 Apt02 可能具有替代 VEGF-A 的潜力。
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