Cancer angiogenesis is mainly initiated by vascular endothelial growth factors (VEGFs). On the basis of the reported crystal structures of three natural ligands (VEGF-A, -B, and PlGF) with the major receptors VEGFR-1 and VEGFR-2, we scanned receptor-binding epitopes of these ligands by designing linear and cyclic peptides with the aim to disrupt the VEGF-A/VEGFR-1 interaction, which is implicated in cancer development. The ability of peptides to inhibit this interaction was evaluated by an ELISA-based assay. Several peptides, especially those mimicking loop 1 (L1) of these ligands that binds primarily to domain D3 of VEGFRs, have demonstrated higher inhibition for VEGF-A/VEGFR-1 binding. They have also shown inhibitory effects on VEGF-induced tube formation in HUVECs (human umbilical vein endothelial cells). These results validate the domain D3 of VEGFRs as an efficient target for the design of VEGFR antagonists.

中文翻译：

---

通过扫描其配体的结合表位鉴定血管内皮生长因子受体1的肽拮抗剂。

癌症血管生成主要由血管内皮生长因子（VEGF）引发。基于已报道的三种具有主要受体VEGFR-1和VEGFR-2的天然配体（VEGF-A，-B和PlGF）的晶体结构，我们通过设计线性和环状肽段扫描了这些配体的受体结合表位目的是破坏与癌症发展有关的VEGF-A / VEGFR-1相互作用。肽抑制这种相互作用的能力通过基于ELISA的测定法进行评估。几种肽，特别是那些模仿这些配体的环1（L1）的肽（主要与VEGFRs的D3结构域结合），已显示出对VEGF-A / VEGFR-1结合的更高抑制作用。他们还显示出对HUVEC（人脐静脉内皮细胞）中VEGF诱导的管形成的抑制作用。