A Combined NMR and Computational Approach to Determine the RGDechi‐hCit‐αvβ3 Integrin Recognition Mode in Isolated Cell Membranes

作者: Biancamaria Farina , Ivan de Paola , Luigi Russo , Domenica Capasso , Annamaria Liguoro

DOI: 10.1002/CHEM.201503126

关键词:

摘要: The critical role of integrins in tumor progression and metastasis has stimulated intense efforts to identify pharmacological agents that can modulate integrin function. In recent years, αv β3 β5 antagonists were demonstrated be effective blocking progression. RGDechi-hCit, a chimeric peptide containing cyclic RGD motif linked an echistatin C-terminal fragment, is able recognize selectively both vitro vivo. High-resolution molecular details the selective recognition are certainly required, nonetheless RGDechi-hCit internalization limited use classical cell NMR experiments. To overcome such limitations, we used WM266 isolated cellular membranes accomplish detailed interaction study that, combined with computational analysis, provides significant structural insights into by RGDechi-hCit. Remarkably, on basis identified determinants, design mutant for integrin.

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