High-Resolution Conformational Analysis of RGDechi-Derived Peptides Based on a Combination of NMR Spectroscopy and MD Simulations(27 views) Acconcia C, Paladino A, Valle MD, Farina B, Del Gatto A, Gaetano SD, Capasso D, Gentile MT, Malgieri G, Isernia C, Saviano M, Fattorusso R, Zaccaro L, Russo L
Department of Environmental, Biological and Pharmaceutical Science and Technology, University of Campania-Luigi Vanvitelli, Via Vivaldi 43, 81100 Caserta, Italy.
Institute of Biostructures and Bioimaging, CNR, Via Castellino 101, 80131 Naples, Italy.
Advanced Accelerator Applications, A Novartis Company, Via Ribes, 510010 Colleretto Giacosa, Italy.
Interdepartmental Center of Bioactive Peptide, University of Naples Federico II, Via Mezzocannone 16, 80134 Naples, Italy.
Center for Life Sciences and Technologies (CESTEV), University of Naples Federico II, Via De Amicis 95, 80145 Naples, Italy.
Institute of Crystallography, CNR, URT Caserta, Via Vivaldi 43, 81100 Caserta, Italy.
References: Not available.
High-Resolution Conformational Analysis of RGDechi-Derived Peptides Based on a Combination of NMR Spectroscopy and MD Simulations
The crucial role of integrin in pathological processes such as tumor progression and metastasis formation has inspired intense efforts to design novel pharmaceutical agents modulating integrin functions in order to provide new tools for potential therapies. In the past decade, we have investigated the biological proprieties of the chimeric peptide RGDechi, containing a cyclic RGD motif linked to an echistatin C-terminal fragment, able to specifically recognize αvβ3 without cross reacting with αvβ5 and αIIbβ3 integrin. Additionally, we have demonstrated using two RGDechi-derived peptides, called RGDechi1-14 and ψRGDechi, that chemical modifications introduced in the C-terminal part of the peptide alter or abolish the binding to the αvβ3 integrin. Here, to shed light on the structural and dynamical determinants involved in the integrin recognition mechanism, we investigate the effects of the chemical modifications by exploring the conformational space sampled by RGDechi1-14 and ψRGDechi using an integrated natural-abundance NMR/MD approach. Our data demonstrate that the flexibility of the RGD-containing cycle is driven by the echistatin C-terminal region of the RGDechi peptide through a coupling mechanism between the N- and C-terminal regions.
High-Resolution Conformational Analysis of RGDechi-Derived Peptides Based on a Combination of NMR Spectroscopy and MD Simulations
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High-Resolution Conformational Analysis of RGDechi-Derived Peptides Based on a Combination of NMR Spectroscopy and MD Simulations