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Combined Use of Oligopeptides, Fragment Libraries, and Natural Compounds: A Comprehensive Approach To Sample the Druggability of Vascular Endothelial Growth Factor
Author(s) -
BayóPuxan Núria,
RodríguezMias Ricard,
Goldflam Michael,
Kotev Martin,
Ciudad Sonia,
Hipolito Christopher J.,
Varese Monica,
Suga Hiroaki,
CamposOlivas Ramón,
Barril Xavier,
Guallar Víctor,
Teixidó Meritxell,
García Jesús,
Giralt Ernest
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201500467
Subject(s) - druggability , vegf receptors , vascular endothelial growth factor , computational biology , kinase insert domain receptor , peptide , protein–protein interaction , oligopeptide , chemistry , peptide library , domain (mathematical analysis) , combinatorial chemistry , biochemistry , biology , vascular endothelial growth factor a , cancer research , peptide sequence , gene , mathematical analysis , mathematics
The modulation of protein–protein interactions (PPIs) is emerging as a highly promising tool to fight diseases. However, whereas an increasing number of compounds are able to disrupt peptide‐mediated PPIs efficiently, the inhibition of domain–domain PPIs appears to be much more challenging. Herein, we report our results related to the interaction between vascular endothelial growth factor (VEGF) and its receptor (VEGFR). The VEGF–VEGFR interaction is a typical domain–domain PPI that is highly relevant for the treatment of cancer and some retinopathies. Our final goal was to identify ligands able to bind VEGF at the region used by the growth factor to interact with its receptor. We undertook an extensive study, combining a variety of experimental approaches, including NMR‐spectroscopy‐based screening of small organic fragments, peptide libraries, and medicinal plant extracts. The key feature of the successful ligands that emerged from this study was their capacity to expose hydrophobic functional groups able to interact with the hydrophobic hot spots at the interacting VEGF surface patch.