Combined Use of Oligopeptides, Fragment Libraries, and Natural Compounds: A Comprehensive Approach To Sample the Druggability of Vascular Endothelial Growth Factor.
Combined Use of Oligopeptides, Fragment Libraries, and Natural Compounds: A Comprehensive Approach To Sample the Druggability of Vascular Endothelial Growth Factor.
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DOI：
10.1002/cmdc.201500467
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发表时间：
2016-04-19
期刊：
影响因子：
3.4
通讯作者：
Giralt, Ernest
中科院分区：
文献类型：
--
作者：
Bayo-Puxan, Nuria;Rodriguez-Mias, Ricard;Goldflam, Michael;Kotev, Martin;Ciudad, Sonia;Hipolito, Christopher J.;Varese, Monica;Suga, Hiroaki;Campos-Olivas, Ramon;Barril, Xavier;Guallar, Victor;Teixido, Meritxell;Garcia, Jesus;Giralt, Ernest
蛋白质-蛋白质相互作用（PPI）的调节正在成为一种非常有前途的对抗疾病的工具。然而，尽管越来越多的化合物能够有效地破坏肽介导的PPI，但结构域-结构域PPI的抑制似乎更具挑战性。在此，我们报告了我们的结果有关血管内皮生长因子（VEGF）及其受体（VEGFR）之间的相互作用。VEGF-VEGFR相互作用是一种典型的结构域-结构域PPI，与癌症和某些视网膜病变的治疗高度相关。我们的最终目标是确定能够在生长因子与其受体相互作用的区域结合VEGF的配体。我们进行了广泛的研究，结合了各种实验方法，包括基于NMR光谱的小有机片段筛选，肽库和药用植物提取物。从本研究中出现的成功配体的关键特征是它们暴露能够与相互作用的VEGF表面补丁处的疏水热点相互作用的疏水官能团的能力。
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.
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影响因子：
5.5
作者：
Borrelli, KW;Vitalis, A;Guallar, V
通讯作者：
Guallar, V
影响因子：
2.7
作者：
Dalvit, C;Pevarello, P;Sundström, M
通讯作者：
Sundström, M
影响因子：
168.9
作者：
Fuchs, Charles S.;Tomasek, Jiri;Tabernero, Josep
通讯作者：
Tabernero, Josep
影响因子：
--
作者：
Crews CM
通讯作者：
Crews CM
影响因子：
20.3
作者：
Brozzo, Maurice S.;Bjelic, Sasa;Ballmer-Hofer, Kurt
通讯作者：
Ballmer-Hofer, Kurt