Molecular modelling of epitopes recognized by neoplastic B lymphocytes in Chronic Lymphocytic Leukemia.
Antineoplastic Agents
/ chemistry
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
Quantitative Structure-Activity Relationship
B cell receptor
CLL
GRID-Pharmacophore
LB-3D-QSAR
Peptides
Phage display
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
01 Jan 2020
01 Jan 2020
Historique:
received:
18
07
2019
revised:
29
10
2019
accepted:
30
10
2019
pubmed:
14
11
2019
medline:
19
2
2020
entrez:
14
11
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31718942
pii: S0223-5234(19)30990-0
doi: 10.1016/j.ejmech.2019.111838
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Epitopes
0
Peptides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
111838Informations de copyright
Copyright © 2019 Elsevier Masson SAS. All rights reserved.