Synthesis of peptide homo‐ and heterodimers as potential mimics of platelet‐derived growth factor BB. Issue 4 (29th February 2020)

• Record Type: Journal Article
• Authors: Stubbing, Louise A.; Kaur, Harveen; Feng, Sheryl X.; Aalderink, Miranda; Dragunow, Michael; Brimble, Margaret A.
• Other Names: Gierasch Lila guestEditor.; Albericio Fernando guestEditor.; Toniolo Claudio guestEditor.
• Is Part Of: Peptide science. Volume 112:Issue 4(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-02-29
• Subjects: CuAAC -- PDGF‐BB -- PDGFRβ -- peptide dimer -- pericyte; Peptides -- Periodicals; 572.6505
• DOI: 10.1002/pep2.24150
• Languages: English
• ISSNs: 2475-8817

Abstract

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. Abstract :