title: Conformational ensembles explored dynamically from disordered peptides targeting chemokine receptor CXCR4.
abstract: This work reports on the design and the synthesis of two short linear peptides both containing a few amino acids with disorder propensity and an allylic ester group at the C-terminal end. Their structural properties were firstly analyzed by means of experimental techniques in solution such as CD and NMR methods that highlighted peptide flexibility. These results were further confirmed by MD simulations that demonstrated the ability of the peptides to assume conformational ensembles. They revealed a network of transient and dynamic H-bonds and interactions with water molecules. Binding assays with a well-known drug-target, i.e., the CXCR4 receptor, were also carried out in an attempt to verify their biological function and the possibility to use the assays to develop new specific targets for CXCR4. Moreover, our data indicate that these peptides represent useful tools for molecular recognition processes in which a flexible conformation is required in order to obtain an interaction with a specific target.
authors.affiliation: Department of Pharmacy University of Naples "Federico II", and CIRPeB, Via Mezzocannone 16, I-80134 Naples, Italy. marian.vincenzi@unina.it.|Institute of Biostructures and Bioimaging (IBB), National Research Council (CNR), Via Mezzocannone 16, I-80134 Naples, Italy. marian.vincenzi@unina.it.|UFR des Sciences Pharmaceutiques-Collège Sciences de la Santé, INSERM U869, Laboratoire ARNA, Université de Bordeaux, 146 rue Léo Saignat, 33076 Bordeaux cedex, France. marian.vincenzi@unina.it.
authors.forename: Marian
authors.initials: M
authors.lastname: Vincenzi
authors.affiliation: Oncology Research Center of Mercogliano (CROM), Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, I-80131 Napoli, Italy. s.costantini@istitutotumori.na.it.
authors.forename: Susan
authors.initials: S
authors.lastname: Costantini
authors.affiliation: Molecular Immunology and Immuneregulation, Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, I-80131 Napoli, Italy. s.scala@istitutotumori.na.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Scala
authors.affiliation: Department of Pharmacy University of Naples "Federico II", and CIRPeB, Via Mezzocannone 16, I-80134 Naples, Italy. diego.tesauro@unina.it.|Institute of Biostructures and Bioimaging (IBB), National Research Council (CNR), Via Mezzocannone 16, I-80134 Naples, Italy. diego.tesauro@unina.it.
authors.forename: Diego
authors.initials: D
authors.lastname: Tesauro
authors.affiliation: Department of Pharmacy University of Naples "Federico II", and CIRPeB, Via Mezzocannone 16, I-80134 Naples, Italy. antonella.accardo@unina.it.|Institute of Biostructures and Bioimaging (IBB), National Research Council (CNR), Via Mezzocannone 16, I-80134 Naples, Italy. antonella.accardo@unina.it.
authors.forename: Antonella
authors.initials: A
authors.lastname: Accardo
authors.affiliation: Institute of Biostructures and Bioimaging (IBB), National Research Council (CNR), Via Mezzocannone 16, I-80134 Naples, Italy. marilisa.leone@cnr.it.
authors.forename: Marilisa
authors.initials: M
authors.lastname: Leone
authors.affiliation: Center of Medical Informatics, AOU, Second University of Naples, I-80138 Napoli, Italy. giovanni.colonna@unina2.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Colonna
authors.affiliation: UFR des Sciences Pharmaceutiques-Collège Sciences de la Santé, INSERM U869, Laboratoire ARNA, Université de Bordeaux, 146 rue Léo Saignat, 33076 Bordeaux cedex, France. jean.guillon@u-bordeaux.fr.
authors.forename: Jean
authors.initials: J
authors.lastname: Guillon
authors.affiliation: Molecular Immunology and Immuneregulation, Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, I-80131 Napoli, Italy. portella@gmail.com.
authors.forename: Luigi
authors.initials: L
authors.lastname: Portella
authors.affiliation: Molecular Immunology and Immuneregulation, Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, I-80131 Napoli, Italy. amt78@libero.it.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Trotta
authors.affiliation: UFR des Sciences Pharmaceutiques-Collège Sciences de la Santé, INSERM U869, Laboratoire ARNA, Université de Bordeaux, 146 rue Léo Saignat, 33076 Bordeaux cedex, France. luisa.ronga@u-bordeaux.fr.
authors.forename: Luisa
authors.initials: L
authors.lastname: Ronga
authors.affiliation: Department of Pharmacy University of Naples "Federico II", and CIRPeB, Via Mezzocannone 16, I-80134 Naples, Italy. filomena.rossi@unina.it.|Institute of Biostructures and Bioimaging (IBB), National Research Council (CNR), Via Mezzocannone 16, I-80134 Naples, Italy. filomena.rossi@unina.it.
authors.forename: Filomena
authors.initials: F
authors.lastname: Rossi
mesh_terms: D002942:Circular Dichroism; D006801:Humans; D006860:Hydrogen Bonding; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D066244:Proton Magnetic Resonance Spectroscopy; D019718:Receptors, CXCR4 / Q000378:metabolism*
chemical_list: C527276:CXCR4 protein, human; D064267:Intrinsically Disordered Proteins; D010455:Peptides; D019718:Receptors, CXCR4
keywords: CD; MD; NMR; chemokine; conformational ensemble; intrinsically disordered protein (IDP); intrinsically disordered region (IDR)