TY - JOUR

T1 - Size and Structure of Empty and Filled Nanocontainer Based on Peptide Dendrimer with Histidine Spacers at Different pH

AU - Bezrodnyi, Valeriy V.

AU - Mikhtaniuk, Sofia E.

AU - Shavykin, Oleg V.

AU - Neelov, Igor M.

AU - Sheveleva, Nadezhda N.

AU - Markelov, Denis A.

N1 - Publisher Copyright: © 2021 by the authors.

PY - 2021/11/1

Y1 - 2021/11/1

N2 - 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

AB - 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

KW - peptide dendrimer

KW - pH responsive spacers

KW - molecular dynamics simulation

KW - histidine–histidine pairing

KW - nanocontainer capacity

KW - Histidine-histidine pairing

KW - Nanocontainer capacity

KW - Molecular dynamics simulation

KW - Peptide dendrimer

KW - PH responsive spacers

KW - POLYMERS

KW - LATTICE NMR RELAXATION

KW - MOLECULAR-DYNAMICS SIMULATION

KW - BROWNIAN DYNAMICS

KW - DELIVERY

KW - GENE

KW - LOCAL DYNAMICS

KW - histidine-histidine pairing

KW - ARGININE

KW - COMPUTER-SIMULATION

KW - LYSINE DENDRIMERS

UR - http://www.scopus.com/inward/record.url?scp=85120700394&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/15f1cc03-ccb5-3eed-b056-7d4a11393a26/

U2 - 10.3390/molecules26216552

DO - 10.3390/molecules26216552

M3 - Article

VL - 26

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 21

M1 - 6552

ER -