Conformational latitude - activity relationship of KPPR tetrapeptide analogues toward their ability to inhibit binding of vascular endothelial growth factor 165 to neuropilin-1
PBN-AR
Instytucja
Instytut Medycyny Doświadczalnej i Klinicznej im. Mirosława Mossakowskiego Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
en
Czasopismo
JOURNAL OF PEPTIDE SCIENCE (20pkt w roku publikacji)
ISSN
1075-2617
EISSN
1099-1387
Wydawca
WILEY-BLACKWELL
DOI
URL
Rok publikacji
2017
Numer zeszytu
6
Strony od-do
445-454
Numer tomu
23
Identyfikator DOI
Liczba arkuszy
1.19
Słowa kluczowe
en
VEGF165
inhibitors of NRP-1
conformational latitude
molecular dynamics
Streszczenia
Język
en
Treść
Neuropilin-1 (NRP-1) has been found to be overexpressed in several kinds of malignant tumors, and it is postulated that in pathological angiogenesis, its interaction with the vascular endothelial growth factor 165 (VEGF(165)) leads to progression of tumor vascularization and growth. Herein, we present synthesis and in vitro evaluation of tetrapeptides with the general sequence KxxR, where xx represents two canonical amino acid residues or a single amino acid possessing hydrocarbon backbone. All synthesized compounds were found to be inhibitors of VEGF(165)/NRP-1 interactions. The rationale behind their design was to elucidate the relationship between the xx flexibility and their inhibitory activity. Detailed molecular dynamics simulations for all synthesized compounds have been performed. A clear and quantitative relationship was found in the peptide analogues: the more flexible is the xx, the less active the analogue is. But surprisingly, highly flexible peptidomimetics with non-natural amino acids (NH2-(CH2)(n)-COOH; n=4,5) residues used possessed higher inhibitory activity than it was expected. Our molecular dynamics study of inhibitor/NRP-1 complexes provides convincing explanations of divergence in the observed inhibitory activity; thus, it might give indication for design of the next generation NRP-1 inhibitors. Copyright (c) 2017 European Peptide Society and John Wiley & Sons, Ltd.
Cechy publikacji
discipline:Biochemia – dziedzina nauk biologicznych
discipline:Biochemia – dziedzina nauk chemicznych
discipline:Biologia medyczna
discipline:Biochemistry – field of biological sciences
discipline:Biochemistry – field of chemical sciences
discipline:Medical biology
Original article
Original article presents the results of original research or experiment.
Oryginalny artykuł naukowy
Oryginalny artykuł naukowy przedstawia rezultaty oryginalnych badań naukowych lub eksperymentu.
Inne
System-identifier
PBN-R:820461
CrossrefMetadata from Crossref logo
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