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Mechanistic basis for the potent anti-angiogenic activity of semaphorin 3F.神经信号蛋白 3F 发挥强大抗血管生成活性的机制基础。
Biochemistry. 2013 Oct 29;52(43):7551-8. doi: 10.1021/bi401034q. Epub 2013 Oct 18.
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Transient mammalian cell transfection with polyethylenimine (PEI).用聚乙烯亚胺(PEI)进行瞬时哺乳动物细胞转染。
Methods Enzymol. 2013;529:227-40. doi: 10.1016/B978-0-12-418687-3.00018-5.
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Effect of C-terminal sequence on competitive semaphorin binding to neuropilin-1.C 末端序列对神经纤毛蛋白-1与竞争 semaphorin 结合的影响。
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Mechanism of selective VEGF-A binding by neuropilin-1 reveals a basis for specific ligand inhibition.神经纤毛蛋白-1 选择性结合 VEGF-A 的机制揭示了特定配体抑制的基础。
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Function of members of the neuropilin family as essential pleiotropic cell surface receptors.神经钙黏蛋白家族成员作为必需的多功能细胞表面受体的功能。
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Studies of vascular endothelial growth factor in asthma and chronic obstructive pulmonary disease.哮喘和慢性阻塞性肺疾病中血管内皮生长因子的研究。
Proc Am Thorac Soc. 2011 Nov;8(6):512-5. doi: 10.1513/pats.201102-018MW.
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Furin processing of semaphorin 3F determines its anti-angiogenic activity by regulating direct binding and competition for neuropilin.弗林蛋白酶对半信号素 3F 的加工通过调节直接结合和与神经纤毛蛋白的竞争来决定其抗血管生成活性。
Biochemistry. 2010 May 18;49(19):4068-75. doi: 10.1021/bi100327r.
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Small molecule inhibitors of the neuropilin-1 vascular endothelial growth factor A (VEGF-A) interaction.神经纤毛蛋白 1-血管内皮生长因子 A(VEGF-A)相互作用的小分子抑制剂。
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9
Structure-function analysis of the antiangiogenic ATWLPPR peptide inhibiting VEGF(165) binding to neuropilin-1 and molecular dynamics simulations of the ATWLPPR/neuropilin-1 complex.抗血管生成ATWLPPR肽抑制VEGF(165)与神经纤毛蛋白-1结合的结构-功能分析及ATWLPPR/神经纤毛蛋白-1复合物的分子动力学模拟
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Structural basis for ligand and heparin binding to neuropilin B domains.配体和肝素与神经纤毛蛋白B结构域结合的结构基础。
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基于微孔板筛选神经纤毛蛋白-2/血管内皮生长因子-C相互作用的小分子抑制剂。

Microplate-based screening for small molecule inhibitors of neuropilin-2/vascular endothelial growth factor-C interactions.

作者信息

Parker Matthew W, Vander Kooi Craig W

机构信息

Center for Structural Biology, Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA.

Center for Structural Biology, Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA.

出版信息

Anal Biochem. 2014 May 15;453:4-6. doi: 10.1016/j.ab.2014.02.017. Epub 2014 Feb 26.

DOI:10.1016/j.ab.2014.02.017
PMID:24583243
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4036672/
Abstract

Vascular endothelial growth factor-C (VEGF-C) is a secreted growth factor essential for lymphangiogenesis. VEGF-C functions in both physiological and pathological lymphangiogenesis, particularly in tumor metastasis, making it an attractive therapeutic target. Members of two families of cell surface receptors transduce VEGF-C signals: neuropilin-2 (Nrp2) and VEGF-receptor (VEGFR)-2/3. Nrp2 is a promising target for inhibition because it is highly expressed in lymphatic vessels. Here we describe a microplate-based assay for discovery of VEGF-C/Nrp2 inhibitors. We optimize this assay for use in screening an inhibitor library and identify three novel Nrp2/VEGF-C binding inhibitors from the National Institutes of Health (NIH) Clinical Collection small molecule library.

摘要

血管内皮生长因子-C(VEGF-C)是一种对淋巴管生成至关重要的分泌型生长因子。VEGF-C在生理性和病理性淋巴管生成中均发挥作用,尤其是在肿瘤转移方面,这使其成为一个有吸引力的治疗靶点。两类细胞表面受体家族的成员可转导VEGF-C信号:神经纤毛蛋白-2(Nrp2)和血管内皮生长因子受体(VEGFR)-2/3。Nrp2是一个很有前景的抑制靶点,因为它在淋巴管中高度表达。在此,我们描述了一种基于微孔板的检测方法,用于发现VEGF-C/Nrp2抑制剂。我们对该检测方法进行了优化,以用于筛选抑制剂文库,并从美国国立卫生研究院(NIH)临床化合物库小分子文库中鉴定出三种新型的Nrp2/VEGF-C结合抑制剂。