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Molecular modelling of epitopes recognized by neoplastic B lymphocytes in Chronic Lymphocytic Leukemia.

Authors
  • Lupia, Antonio1
  • Mimmi, Selena2
  • Iaccino, Enrico2
  • Maisano, Domenico2
  • Moraca, Federica3
  • Talarico, Carmine4
  • Vecchio, Eleonora2
  • Fiume, Giuseppe2
  • Ortuso, Francesco5
  • Scala, Giuseppe2
  • Quinto, Ileana6
  • Alcaro, Stefano7
  • 1 Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus "S. Venuta", Viale Europa, Germaneto, 88100, Catanzaro, Italy; Net4Science srl, University "Magna Græcia", Campus Salvatore Venuta, Viale Europa, Catanzaro, 88100, Italy. Electronic address: [email protected] , (Italy)
  • 2 Department of Experimental and Clinical Medicine, "Magna Græcia" University of Catanzaro, Campus "S. Venuta", Viale Europa, Germaneto, 88100, Catanzaro, Italy. , (Italy)
  • 3 Net4Science srl, University "Magna Græcia", Campus Salvatore Venuta, Viale Europa, Catanzaro, 88100, Italy; University "Federico II" of Naples, Department of Pharmacy, Via D. Montesano 49, Naples, 80131, Italy. , (Italy)
  • 4 Dompé farmaceutici S.p.A., Via Pietro Castellino 111, Naples, 80131, Italy. , (Italy)
  • 5 Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus "S. Venuta", Viale Europa, Germaneto, 88100, Catanzaro, Italy; Net4Science srl, University "Magna Græcia", Campus Salvatore Venuta, Viale Europa, Catanzaro, 88100, Italy. , (Italy)
  • 6 Department of Experimental and Clinical Medicine, "Magna Græcia" University of Catanzaro, Campus "S. Venuta", Viale Europa, Germaneto, 88100, Catanzaro, Italy. Electronic address: [email protected] , (Italy)
  • 7 Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus "S. Venuta", Viale Europa, Germaneto, 88100, Catanzaro, Italy; Net4Science srl, University "Magna Græcia", Campus Salvatore Venuta, Viale Europa, Catanzaro, 88100, Italy. Electronic address: [email protected] , (Italy)
Type
Published Article
Journal
European journal of medicinal chemistry
Publication Date
Jan 01, 2020
Volume
185
Pages
111838–111838
Identifiers
DOI: 10.1016/j.ejmech.2019.111838
PMID: 31718942
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Identification of epitopes recognized by tumour B cells could provide insights into the molecular mechanisms of B cell tumorigenesis through aberrant B cell receptor (BCR) signalling. Here, we analysed the structure of eleven peptides binders of BCRs expressed in Chronic Lymphocytic Leukemia (CLL) patients in order to identify the chemical features required for cross-reactive binding to different CLL clonotypes. Four cross-reactive (CR) and seven no-cross-reactive (NCR) peptides were analysed by means of GRID molecular interaction fields, ligand-based pharmacophore and 3D-QSAR approaches. Based on pharmacophore model, two peptides were generated by specific amino acids substitutions of the parental NCR peptides; these new peptides resumed the common chemical features of CR peptides and bound the CLL BCR clonotypes recognized by CR peptides and parental NCR peptides. Thus, our computational approach guided the pharmacophore modelling of CR peptides. In perspective, peptide binders of CLL BCR clonotypes could represent a powerful tool for computational modelling of epitopes recognized by tumour B cells clones. Copyright © 2019 Elsevier Masson SAS. All rights reserved.

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