title: Design, synthesis and in vitro biological evaluation of a small cyclic peptide as inhibitor of vascular endothelial growth factor binding to neuropilin-1.
abstract: Neuropilin-1 (NRP-1) is a co-receptor of VEGFR (vascular endothelial growth factor receptor), but it is also suggested that NRP-1 in tumour cells may serve as a separate receptor for VEGF165. Therefore molecules interfering with VEGF165 binding to NRP-1 seem to be promising candidates as new anti-angiogenic and anti-tumour drugs. Here, we report the design, synthesis, biological evaluation and molecular modelling of the small cyclic peptide, which shows a good inhibitory effect on VEGF165/NRP-1 binding (IC50=0.18μM). The reported compound could be considered as one of the smallest cyclic peptides (MW=510) interfering with VEGF165/NRP-1 binding presented up to now.
authors.affiliation: Faculty of Chemistry, University of Warsaw, 02-093 Warsaw, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Grabowska
authors.affiliation: Faculty of Chemistry, University of Warsaw, 02-093 Warsaw, Poland.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Puszko
authors.affiliation: Department of Neuropeptides, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warsaw, Poland.
authors.forename: Piotr F J
authors.initials: PFJ
authors.lastname: Lipiński
authors.affiliation: Department of Neuropeptides, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warsaw, Poland.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Laskowska
authors.affiliation: Faculty of Chemistry, University of Warsaw, 02-093 Warsaw, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Wileńska
authors.affiliation: Faculty of Chemistry, University of Warsaw, 02-093 Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Witkowska
authors.affiliation: Faculty of Chemistry, University of Warsaw, 02-093 Warsaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Misicka
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D039942:Neuropilin-1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D010456:Peptides, Cyclic; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1
keywords: Angiogenesis; Cyclic peptide; Neuropilin; VEGF(165)