The energy landscape of a selective tumor-homing pentapeptide
| Autor: | David Zanuy, Alejandra Flores-Ortega, Ruth Nussinov, Jordi Casanovas, David Curcó, Carlos Alemán |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Phage display
Time Factors Molecular Sequence Data Glutamic Acid Peptide Arginine Pentapeptide repeat Article Protein Structure Secondary Protein structure Materials Chemistry Side chain Computer Simulation Amino Acid Sequence Physical and Theoretical Chemistry Binding site Peptide sequence chemistry.chemical_classification Binding Sites Lysine Energy landscape Water Peptide Fragments Surfaces Coatings and Films Neoplasm Proteins Solutions Biochemistry chemistry Biophysics Nanoparticles Thermodynamics Oligopeptides |
| Popis: | Recently, a potentially powerful strategy based on the of phage-display libraries has been presented to target tumors via homing peptides attached to nanoparticles. The Cys-Arg-Glu-Lys-Ala (CREKA) peptide sequence has been identified as a tumor-homing peptide that binds to clotted plasmas proteins present in tumor vessels and interstitium. The aim of this work consists of mapping the conformational profile of CREKA to identify the bioactive conformation. For this purpose, a conformational search procedure based on modified Simulated Annealing combined with Molecular Dynamics was applied to three systems that mimic the experimentally used conditions: (i) the free peptide; (ii) the peptide attached to a nanoparticle; and (iii) the peptide inserted in a phage display protein. In addition, the free peptide was simulated in an ionized aqueous solution environment, which mimics the ionic strength of the physiological medium. Accessible minima of all simulated systems reveal a multiple interaction pattern involving the ionized side chains of Arg, Glu and Lys, which induces a β-turn motif in the backbone observed in all simulated CREKA systems. |
| Databáze: | OpenAIRE |
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