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

Eur J Med Chem. 2020 Jan 1;185:111838. doi: 10.1016/j.ejmech.2019.111838. Epub 2019 Nov 1.


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.

Keywords: B cell receptor; CLL; GRID-Pharmacophore; LB-3D-QSAR; Peptides; Phage display.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • B-Lymphocytes / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Epitopes / analysis*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Models, Molecular
  • Molecular Structure
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Quantitative Structure-Activity Relationship


  • Antineoplastic Agents
  • Epitopes
  • Peptides