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Synthesis of peptide homo‐ and heterodimers as potential mimics of platelet‐derived growth factor BB

Synthesis of peptide homo‐ and heterodimers as potential mimics of platelet‐derived growth factor BB 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Peptide Science Wiley

Synthesis of peptide homo‐ and heterodimers as potential mimics of platelet‐derived growth factor BB

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References (37)

Publisher
Wiley
Copyright
© 2020 Wiley Periodicals LLC.
eISSN
2475-8817
DOI
10.1002/pep2.24150
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Peptide ScienceWiley

Published: Jul 1, 2020

Keywords: ; ; ; ;

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