摘要
血管内皮生长因子-血管内皮生长因子受体2(VEGF-VEGFR2)激发的信号转导通路在肿瘤血管生成中起着重要作用。VEGFR2的有效拮抗剂可作为恶性肿瘤治疗的有效药物。研究中,我们通过细菌显示技术获得了对VEGFR2具有高亲和力的特异性结合肽。保守的基序在这些肽序列中被发现。一个特定的肽VRBP1 (YDGNSFYEMWGVKPASES)由偏性细菌肽库筛选鉴定,其理化特征得到进一步表征。表面等离子共振(SPR)试验结果表明VRBP1解离常数(KD)的值是228.3 nM ,而且这个肽与VEGF 竞争结合VEGFR2。微粒与VRBP1结合能够识别在表面表达VEGFR2的人脐静脉内皮细胞(HUVEC)。体内试验可进一步得出VRBP1的治疗效果。VRBP1可导致H460异种移植肿瘤体积明显减小。免疫组织化学试验的结果表明VRBP1治疗组的CD31阳性信号均低于对照组。这些数据强调了VEGFR2结合肽作为癌症诊断和治疗的有效分子的可能性。
关键词: 血管生成,细菌表面展示,癌症诊断,癌症治疗,肽,血管内皮生长因子受体2(VEGFR2).
图形摘要
Current Cancer Drug Targets
Title:Identification of VEGFR2-Binding Peptides Using High Throughput Bacterial Display Methods and Functional Assessment
Volume: 15 Issue: 2
Author(s): Kefeng Pu, Lihua Yuan, Lisha Chen, Anxin Wang, Xuan Zhou, Hailu Zhang and Yimin Zhu
Affiliation:
关键词: 血管生成,细菌表面展示,癌症诊断,癌症治疗,肽,血管内皮生长因子受体2(VEGFR2).
摘要: The signal transduction pathway initiated by vascular endothelial growth factor-vascular endothelial growth factor receptor 2 (VEGF-VEGFR2) plays an important role in the angiogenesis of tumors. The effective antagonists of VEGFR2 would behave as potent drugs for the treatment of malignant cancers. In our study, specific binding peptides with high affinity to VEGFR2 were obtained through bacterial display technology. Conserved motif (FF/YEXWGVK) among those peptide sequences was discovered. One of the selected peptides, VRBP1 (YDGNSFYEMWGVKPASES) was identified by screening the biased bacterial peptide library and its physiochemical feature was further characterized. The results of surface plasmon resonance (SPR) assay indicated that the dissociation constant (KD) value of VRBP1 was 228.3 nM and this peptide competed with VEGF binding to VEGFR2. Particles conjugated with VRBP1 could recognize the human umbilical vein endothelial cells (HUVEC) which express VEGFR2 on the surface. Further therapeutic effect of VRBP1 was examined by in vivo experiments. VRBP1 could result in a significant decrease in tumor size of H460 xenografts. The results from the immunohistochemical assay showed that CD31 positive signals in VRBP1-treated group were fewer than those in the control ones. These data highlighted the potential of VEGFR2-binding peptides as effective molecules for cancer diagnosis and therapy.
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Cite this article as:
Kefeng Pu, Lihua Yuan, Lisha Chen, Anxin Wang, Xuan Zhou, Hailu Zhang and Yimin Zhu , Identification of VEGFR2-Binding Peptides Using High Throughput Bacterial Display Methods and Functional Assessment, Current Cancer Drug Targets 2015; 15 (2) . https://dx.doi.org/10.2174/156800961502150320112339
DOI https://dx.doi.org/10.2174/156800961502150320112339 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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