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Nucleosome binding peptide presents laudable biophysical and in vivo effects.

Authors
  • Teles, Kaian1
  • Fernandes, Vinicius2
  • Silva, Isabel1
  • Leite, Manuela1
  • Grisolia, Cesar3
  • Lobbia, Vincenzo R4
  • van Ingen, Hugo4
  • Honorato, Rodrigo5
  • Lopes-de-Oliveira, Paulo5
  • Treptow, Werner6
  • Santos, Guilherme7
  • 1 Laboratório de Farmacologia Molecular, Departamento de Farmácia, Universidade de Brasília, Brasília, 70919-970, Brazil. , (Brazil)
  • 2 Laboratório de Farmacologia Molecular, Departamento de Farmácia, Universidade de Brasília, Brasília, 70919-970, Brazil; Laboratório de Biologia Teórica e Computacional, Departamento de Biologia Celular, Universidade de Brasília, DF, 70910-900, Brasília, Brazil. , (Brazil)
  • 3 Laboratório de Genética Toxicológica, Departamento de Genética e Morfologia, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, Brazil. , (Brazil)
  • 4 NMR Spectroscopy Group, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 CH, Utrecht, the Netherlands. , (Netherlands)
  • 5 Laboratório Nacional de Biociências (LNBio), Campinas, SP, Brazil. , (Brazil)
  • 6 Laboratório de Biologia Teórica e Computacional, Departamento de Biologia Celular, Universidade de Brasília, DF, 70910-900, Brasília, Brazil. , (Brazil)
  • 7 Laboratório de Farmacologia Molecular, Departamento de Farmácia, Universidade de Brasília, Brasília, 70919-970, Brazil. Electronic address: [email protected] , (Brazil)
Type
Published Article
Journal
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Publication Date
Jan 01, 2020
Volume
121
Pages
109678–109678
Identifiers
DOI: 10.1016/j.biopha.2019.109678
PMID: 31810135
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Chromatin state is highly dependent on the nucleosome binding proteins. Herein, we used a multipronged approach employing biophysical and in vivo experiments to characterize the effects of Nucleosome Binding Peptides (NBPeps) on nucleosome and cell activity. We performed a series of structure-based calculations on the nucleosome surface interaction with GMIP1 (a novel NBPep generated in silico), and HMGN2 (nucleosome binding motif of HMGN2), which contains sites that bind DNA and the acid patch, and also LANA and H4pep (nucleosome binding motif of H4 histone tail) that only bind to the acidic patch. Biochemical assays shows that H4pep, but not HMGN2, GMIP1 and LANA, is highly specific for targeting the nucleosome, with important effects on the final nucleosome structure and robust in vivo effects. These findings suggest that NBPeps might have important therapeutic implications and relevance as tools for chromatin investigation. Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

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