Membrane adsorption and binding, cellular uptake and cytotoxicity of cell-penetrating peptidomimetics with α-peptide/β-peptoid backbone: effects of hydrogen bonding and α-chirality in the β-peptoid residues
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Membrane adsorption and binding, cellular uptake and cytotoxicity of cell-penetrating peptidomimetics with α-peptide/β-peptoid backbone : effects of hydrogen bonding and α-chirality in the β-peptoid residues. / Jing, Xiaona; Yang, Mingjun; Kasimova, Marina Robertovna; Malmsten, Martin; Franzyk, Henrik; Jørgensen, Lene; Foged, Camilla; Nielsen, Hanne Mørck.
I: BBA General Subjects, Bind 1818, Nr. 11, 2012, s. 2660-2668.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Membrane adsorption and binding, cellular uptake and cytotoxicity of cell-penetrating peptidomimetics with α-peptide/β-peptoid backbone
T2 - effects of hydrogen bonding and α-chirality in the β-peptoid residues
AU - Jing, Xiaona
AU - Yang, Mingjun
AU - Kasimova, Marina Robertovna
AU - Malmsten, Martin
AU - Franzyk, Henrik
AU - Jørgensen, Lene
AU - Foged, Camilla
AU - Nielsen, Hanne Mørck
N1 - Copyright © 2012 Elsevier B.V. All rights reserved.
PY - 2012
Y1 - 2012
N2 - Cell-penetrating peptides (CPPs) provide a promising approach for enhancing intracellular delivery of therapeutic biomacromolecules by increasing transport through membrane barriers. Here, proteolytically stable cell-penetrating peptidomimetics with α-peptide/β-peptoid backbone were studied to evaluate the effect of α-chirality in the β-peptoid residues and the presence of guanidinium groups in the α-amino acid residues on membrane interaction. The molecular properties of the peptidomimetics in solution (surface and intramolecular hydrogen bonding, aqueous diffusion rate and molecular size) were studied along with their adsorption to lipid bilayers, cellular uptake, and toxicity. The surface hydrogen bonding ability of the peptidomimetics reflected their adsorbed amounts onto lipid bilayers as well as with their cellular uptake, indicating the importance of hydrogen bonding for their membrane interaction and cellular uptake. Ellipsometry studies further demonstrated that the presence of chiral centers in the β-peptoid residues promotes a higher adsorption to anionic lipid bilayers, whereas circular dichroism results showed that α-chirality influences their overall mean residue ellipticity. The presence of guanidinium groups and α-chiral β-peptoid residues was also found to have a significant positive effect on uptake in living cells. Together, the findings provide an improved understanding on the behavior of cell-penetrating peptidomimetics in the presence of lipid bilayers and live cells.
AB - Cell-penetrating peptides (CPPs) provide a promising approach for enhancing intracellular delivery of therapeutic biomacromolecules by increasing transport through membrane barriers. Here, proteolytically stable cell-penetrating peptidomimetics with α-peptide/β-peptoid backbone were studied to evaluate the effect of α-chirality in the β-peptoid residues and the presence of guanidinium groups in the α-amino acid residues on membrane interaction. The molecular properties of the peptidomimetics in solution (surface and intramolecular hydrogen bonding, aqueous diffusion rate and molecular size) were studied along with their adsorption to lipid bilayers, cellular uptake, and toxicity. The surface hydrogen bonding ability of the peptidomimetics reflected their adsorbed amounts onto lipid bilayers as well as with their cellular uptake, indicating the importance of hydrogen bonding for their membrane interaction and cellular uptake. Ellipsometry studies further demonstrated that the presence of chiral centers in the β-peptoid residues promotes a higher adsorption to anionic lipid bilayers, whereas circular dichroism results showed that α-chirality influences their overall mean residue ellipticity. The presence of guanidinium groups and α-chiral β-peptoid residues was also found to have a significant positive effect on uptake in living cells. Together, the findings provide an improved understanding on the behavior of cell-penetrating peptidomimetics in the presence of lipid bilayers and live cells.
KW - Adsorption
KW - Calorimetry
KW - Circular Dichroism
KW - HeLa Cells
KW - Humans
KW - Hydrogen Bonding
KW - Liposomes
KW - Models, Molecular
KW - Molecular Dynamics Simulation
KW - Peptidomimetics
KW - Peptoids
KW - Protein Binding
KW - Stereoisomerism
U2 - 10.1016/j.bbamem.2012.05.003
DO - 10.1016/j.bbamem.2012.05.003
M3 - Journal article
C2 - 22609348
VL - 1818
SP - 2660
EP - 2668
JO - B B A - General Subjects
JF - B B A - General Subjects
SN - 0304-4165
IS - 11
ER -
ID: 104572616