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Structure-activity relationship studies and biological properties evaluation of peptidic NRP-1 ligands: Investigation of N-terminal cysteine importance

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cris.lastimport.scopus2024-02-12T20:52:16Z
dc.abstract.enNeuropilin-1 (NRP-1) is a major co-receptor of vascular endothelial growth factor receptor-2 (VEGFR-2). It may also stimulate tumour growth and metastasis independently of VEGF-A165. These functions make VEGF-A165/NRP-1 complex formation and its inhibition of great interest, where NRP-1 is the target for which effective ligands are sought. Design of peptide-like inhibitors represent a strategy with great potential in the treatment of NRP-1-related disorders. Here, we present the synthesis, molecular modelling, structure-activity relationship studies as well as biological evaluation of peptides with the branched sequences H2N-X-Lys(hArg)-Dab-Oic-Arg-OH and H2N-Lys(X-hArg)-Dab-Oic-Arg-OH. Two of the designed peptides, in which Cys was inserted in X position, expressed high affinity (∼40 nM value) for NRP-1 and were resistant to enzymatic digestion in human serum. Moreover, peptide/NRP-1 complex promoted fast intracytoplasmic protein trafficking towards the plasma membrane in breast cancer cells. Our results suggest that these compounds might be good candidates for further development of VEGF-A165/NRP-1 inhibitors.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorMisicka-Kęsik, Aleksandra
dc.contributor.authorLepelletier, Yves
dc.contributor.authorHopfgartner, Gérard
dc.contributor.authorHermine, Olivier
dc.contributor.authorSosnowski, Piotr
dc.contributor.authorPuszko, Anna
dc.date.accessioned2024-01-26T08:21:45Z
dc.date.available2024-01-26T08:21:45Z
dc.date.copyright2023-09-22
dc.date.issued2023
dc.description.accesstimeAT_PUBLICATION
dc.description.financeNie dotyczy
dc.description.versionFINAL_PUBLISHED
dc.description.volume94
dc.identifier.doi10.1016/J.BMC.2023.117482
dc.identifier.issn0968-0896
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/120905
dc.identifier.weblinkhttps://api.elsevier.com/content/article/PII:S0968089623003309?httpAccept=text/xml
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofBioorganic and Medicinal Chemistry
dc.relation.pages117482
dc.rightsCC-BY
dc.sciencecloudnosend
dc.subject.enNeuropilin-1
dc.subject.enVEGF-A165
dc.subject.enVEGF-A165/NRP-1 complex
dc.subject.enProtein-ligand interaction
dc.subject.enPeptide ligands
dc.titleStructure-activity relationship studies and biological properties evaluation of peptidic NRP-1 ligands: Investigation of N-terminal cysteine importance
dc.typeJournalArticle
dspace.entity.typePublication