Sam domain-based stapled peptides: Structural analysis and interaction studies with the Sam domains from the EphA2 receptor and the lipid phosphatase Ship2(181 visite) Mercurio FA, Pirone L, Di Natale C, Marasco D, Pedone EM, Leone M
Tipo di articolo: Journal Article, Research Support, Non-U. S. Gov'T,
Impact factor: 3.9, Impact factor a 5 anni: 3.39
Url: Non disponibile.
Parole chiave: Cancer, Epha2, Ppi Inhibitors, Sam Domains, Stapled Peptides, Amino Acid Sequence
, Drug Discovery
, Models, Molecular
, Peptides Chemistry Pharmacology
, Phosphatidylinositol-3, 5-Trisphosphate 5-Phosphatases Chemistry Metabolism
, Protein Binding Drug Effects
, Protein Interaction Maps Drug Effects
, Receptor, Epha2 Chemistry Metabolism
, Sterile Alpha Motif Drug Effects,
*** IBB - CNR *** Institute of Biostructures and Bioimaging (CNR), Naples, Italy InterUniversity Research Centre on Bioactive Peptides (CIRPEB), University of Naples Federico II, Naples, Italy.
Sam (Sterile alpha motif) domains represent small helical protein-protein interaction modules which play versatile functions in different cellular processes. The Sam domain from the EphA2 receptor binds the Sam domain of the lipid phosphatase Ship2 and this interaction modulates receptor endocytosis and degradation primarily generating pro-oncogenic effects in cell. To identify molecule antagonists of the EphA2-Sam/Ship2-Sam complex with anti-cancer activity, we focused on hydrocarbon helical stapled peptides. EphA2-Sam and one of its interactors (i.e., the first Sam domain of the adaptor protein Odin) were used as model systems for peptide design. Increase in helicity in the stapled peptides, with respect to the corresponding linear/native-like regions, was proved by structural studies conducted through CD (Circular Dichroism) and NMR (Nuclear Magnetic Resonance). Interestingly, interaction assays by means of NMR, SPR (Surface Plasmon Resonance) and MST (MicroScale Thermophoresis) techniques led to the discovery of a novel ligand of Ship2-Sam.<br>