Pericyte loss is correlated with blood‐brain barrier leakage in neurological disorders such as Alzheimer's disease. The platelet‐derived growth factor receptor β (PDGFRβ)/platelet‐derived growth factor BB (PDGF‐BB) signalling pathway is key to the regulation of pericyte survival and proliferation. A series of peptide dimers mimicking the ligand PDGF‐BB were prepared in the hope of stimulating PDGFRβ internalisation and activation of this pathway. Copper‐catalysed azide‐alkyne cycloaddition of peptide monomers with PEGylated linkers of varying length afforded the desired peptide dimers. Evaluation of the peptide dimers in human brain pericyte assays revealed no effect on PDGFRβ internalisation nor cell proliferation at concentrations <10 μM. The peptide dimers also did not act as antagonists at PDGFRβ at concentrations <10 μM.

中文翻译：

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肽同源和异二聚体的合成作为血小板衍生生长因子BB的潜在模拟物

在诸如阿尔茨海默氏病等神经系统疾病中，周细胞的丢失与血脑屏障的泄漏有关。血小板衍生的生长因子受体（PDGFRβ）/血小板衍生的生长因子BB（PDGF-BB）信号通路是调节周细胞存活和增殖的关键。制备了一系列模拟配体PDGF-BB的肽二聚体，以期刺激PDGFRβ的内在化和该途径的激活。铜催化的叠氮基-炔烃环化肽单体与不同长度的PEG化接头的加成反应提供了所需的肽二聚体。在人脑周细胞测定中对肽二聚体的评估显示，浓度小于10μM时，对PDGFRβ的内在化和细胞增殖均无影响。浓度<10μM时，肽二聚体也不能作为PDGFRβ的拮抗剂。