Design and analysis of EphA2-SAM peptide ligands: A multi-disciplinary screening approach(270 views) Mercurio FA, Di Natale C, Pirone L, Marasco D, Calce E, Vincenzi M, Pedone EM, De Luca S, Leone M
Institute of Biostructures and Bioimaging (CNR), Naples, Italy; InterUniversity Research Centre on Bioactive Peptides (CIRPEB), University of Naples Federico II, Naples, Italy., University of Naples Federico II, Department of Pharmacy, Naples, Italy., Institute of Biostructures and Bioimaging (CNR), Naples, Italy., Institute of Biostructures and Bioimaging (CNR), Naples, Italy; InterUniversity Research Centre on Bioactive Peptides (CIRPEB), University of Naples Federico II, Naples, Italy; University of Naples Federico II, Department of Pharmacy, Naples, Italy., Institute of Biostructures and Bioimaging (CNR), Naples, Italy; InterUniversity Research Centre on Bioactive Peptides (CIRPEB), University of Naples Federico II, Naples, Italy. Electronic address: marilisa.leone@cnr.it.,
InterUniversity Research Centre on Bioactive Peptides (CIRPEB), University of Naples Federico II, Naples, Italy.
University of Naples Federico II, Department of Pharmacy, Naples, Italy.
References: Not available.
Design and analysis of EphA2-SAM peptide ligands: A multi-disciplinary screening approach
EphA2 receptor plays a critical and debatable function in cancer and is considered a target in drug discovery. Lately, there has been a growing interest in its cytosolic C-terminal SAM domain (EphA2-SAM) as it engages protein modulators of receptor endocytosis and stability. Interestingly, EphA2-SAM binds the SAM domain from the lipid phosphatase Ship2 (Ship2-SAM) mainly producing pro-oncogenic outcomes. In an attempt to discover novel inhibitors of the EphA2-SAM/Ship2-SAM complex with possible anticancer properties, we focused on the central region of Ship2-SAM (known as Mid-Loop interface) responsible for its binding to EphA2-SAM. Starting from the amino acid sequence of the Mid-Loop interface virtual peptide libraries were built through ad hoc inserted mutations with either l- or d- amino acids and screened against EphA2-SAM by docking techniques. A few virtual hits were synthesized and experimentally tested by a variety of direct and competition-type interaction assays relying on NMR (Nuclear Magnetic Resonance), SPR (Surface Plasmon Resonance), MST (Microscale Thermophoresis) techniques. These studies guided the discovery of an original EphA2-SAM ligand antagonist of its interaction with Ship2-SAM.
Design and analysis of EphA2-SAM peptide ligands: A multi-disciplinary screening approach
Kállay C, Dávid A, Timári S, Nagy EM, Sanna D, Garribba E, Micera G, De Bona P, Pappalardo G, Rizzarelli E, Sóvágó I * Copper(II) complexes of rat amylin fragments(464 views) Dalton T (ISSN: 1477-9234, 1477-9226, 1477-9234electronic), 2011 Oct 14; 40(38): 9711-9721. Impact Factor:3.838 ViewExport to BibTeXExport to EndNote
Aloj L, Aurilio M, Rinaldi V, D'Ambrosio L, Tesauro D, Peitl PK, Maina T, Mansi R, Von Guggenberg E, Joosten L, Sosabowski JK, Breeman WA, De Blois E, Koelewijn S, Melis M, Waser B, Beetschen K, Reubi JC, De Jong M * The EEE project(532 views) Proc Int Cosm Ray Conf Icrc Universidad Nacional Autonoma De Mexico, 2007; 5(HEPART2): 977-980. Impact Factor:0 ViewExport to BibTeXExport to EndNote