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Int. J. Mol. Sci. 2015, 16(6), 12159-12173; doi:10.3390/ijms160612159

Conformational Ensembles Explored Dynamically from Disordered Peptides Targeting Chemokine Receptor CXCR4

1
Department of Pharmacy University of Naples "Federico II", and CIRPeB, Via Mezzocannone 16, I-80134 Naples, Italy
2
Institute of Biostructures and Bioimaging (IBB), National Research Council (CNR), Via Mezzocannone 16, I-80134 Naples, Italy
3
Oncology Research Center of Mercogliano (CROM), Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, I-80131 Napoli, Italy
4
Molecular Immunology and Immuneregulation, Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, I-80131 Napoli, Italy
5
Center of Medical Informatics, AOU, Second University of Naples, I-80138 Napoli, Italy
6
UFR des Sciences Pharmaceutiques—Collège Sciences de la Santé, INSERM U869, Laboratoire ARNA, Université de Bordeaux, 146 rue Léo Saignat, 33076 Bordeaux cedex, France
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Lukasz Kurgan
Received: 2 March 2015 / Accepted: 20 May 2015 / Published: 28 May 2015
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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. View Full-Text
Keywords: intrinsically disordered protein (IDP); intrinsically disordered region (IDR); conformational ensemble; MD; NMR; CD; chemokine intrinsically disordered protein (IDP); intrinsically disordered region (IDR); conformational ensemble; MD; NMR; CD; chemokine
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Vincenzi, M.; Costantini, S.; Scala, S.; Tesauro, D.; Accardo, A.; Leone, M.; Colonna, G.; Guillon, J.; Portella, L.; Trotta, A.M.; Ronga, L.; Rossi, F. Conformational Ensembles Explored Dynamically from Disordered Peptides Targeting Chemokine Receptor CXCR4. Int. J. Mol. Sci. 2015, 16, 12159-12173.

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