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Novel peptide dendrimer with Lys-2His repeating units was recently synthesized, studied by NMR (Molecules, 2019, 24, 2481) and tested as a nanocontainer for siRNA delivery (Int. J. Mol. Sci., 2020, 21, 3138). Histidine amino acid residues were inserted in the spacers of this dendrimer. Increase of their charge with a pH decrease turns a surface-charged dendrimer into a volume-charged one and should change all properties. In this paper, the molecular dynamics simulation method was applied to compare the properties of the dendrimer in water with explicit counterions at two different pHs (at normal pH with neutral histidines and at low pH with fully protonated histidines) in a wide interval of temperatures. We obtained that the dendrimer at low pH has essentially larger size and size fluctuations. The electrostatic properties of the dendrimers are different but they are in good agreement with the theoretical soft sphere model and practically do not depend on temperature. We have shown that the effect of pairing of side imidazole groups is much stronger in the dendrimer with neutral histidines than in the dendrimer with protonated histidines. We also demonstrated that the capacity of a nanocontainer based on this dendrimer with protonated histidines is significantly larger than that of a nanocontainer with neutral histidines
Original languageEnglish
Article number6552
Number of pages23
JournalMolecules
Volume26
Issue number21
DOIs
StatePublished - 1 Nov 2021

    Research areas

  • peptide dendrimer, pH responsive spacers, molecular dynamics simulation, histidine–histidine pairing, nanocontainer capacity, Histidine-histidine pairing, Nanocontainer capacity, Molecular dynamics simulation, Peptide dendrimer, PH responsive spacers, POLYMERS, LATTICE NMR RELAXATION, MOLECULAR-DYNAMICS SIMULATION, BROWNIAN DYNAMICS, DELIVERY, GENE, LOCAL DYNAMICS, histidine-histidine pairing, ARGININE, COMPUTER-SIMULATION, LYSINE DENDRIMERS

    Scopus subject areas

  • Drug Discovery
  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Physical and Theoretical Chemistry
  • Pharmaceutical Science
  • Organic Chemistry

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