VEGF-B线性模拟肽的设计、合成和抗血管新生活性研究

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关键词：抗血管新生；血管内皮生长因子受体；多肽抑制剂;计算机辅助药物设计;人脐静脉内皮细胞中图分类号：TQ464.7；R914 文献标志码：A 文章编号：1673-3851（2025）11-0864-08引文格式：，，.VEGF-B线性模拟肽的设计、合成和抗血管新生活性研究[J]．浙江理工大学学报（自然科学），2025，53（6）：864-871.Reference Format：MENG Xiaoli，LIULili，WANG Lei.Design，synthesis，and anti-angiogenic activity evaluationof alinear peptide mimicking VEGF-B[J]. Journal of Zhejiang Sci-Tech University，2025，53（6）：864-871.

Design，synthesis，and anti-angiogenic activity evaluation of a linear peptide mimicking VEGF-B

MENG Xiaoli ，LIU Lili，WANG Lei （College of Life Sciences and Medicine， Zhejiang Sci-Tech University，Hangzhou 3loo18，China）

Abstract： Anti-angiogenic inhibitors that target the binding of vascular endothelial growth factor （VEGF） to vascular endothelial growth factor receptors （VEGFRs） have demonstrated significant clinical value in the treatment of tumors and retinal macular diseases. To further explore novel VEGFR-targeting inhibitors，this study employed computer-aided drug design （CADD） to analyze the interaction between VEGF-B and VEGFR1. The study also designed peptide inhibitor by mimicking key binding sites of VEGF-B，synthesizing a linear VEGF-B mimetic peptide named Peptide 1. The targeting specificity and anti-angiogenic activity of Peptide 1 were subsequently evaluated through cel experiments. The results showed that Peptide 1 had an amino acid sequence of Leu-Thr-Val-Glu-Leu-Met-Gly-Thr-Val-Ala-Lys-GlnLeu-Val-Pro-Ser ⋅NH2 ，a purity of 97.3% and a yield of 10.3% . Peptide 1 specifically inhibited the binding of VEGF to VEGFR1，with a half maximal inhibitory concentration （ IC50 ）value of 21.9μmolMoreover，Peptide 1 significantly suppressed the proliferation，migration，and tube formation of human umbilicalvein endothelial cels（HUVECs） in cell assays. This study demonstrates the feasibility and application value of designing VEGFR-targeting peptide inhibitors based on the structure of VEGF-B，and provides a scientific basis for the development of novel peptide-based anti-angiogenic inhibitors.

Key words： anti-angiogenesis； vascular endothelial growth factor receptors； peptide inhibitor;computer-aided drug design;human umbilical vein endothelial cells

0 引言

抗血管新生药物是抗肿瘤靶向药物的重要组成部分，其作用机制明确，主要通过干预血管内皮生长因子（Vascular endothelial growth factor，VEGF）和血管内皮生长因子受体（Vascularendothelialgrowthfactorreceptor，VEGFR）介导的信号通路，抑制新生血管的形成，阻断肿瘤组织的营养和氧气供给，进而抑制肿瘤的生长与转移[1-2]。（剩余11843字）