Lysine-based dendrimer with double arginine residues

Sheveleva, Nadezhda N.; Markelov, Denis A.; Vovk, Mikhail A.; Mikhailova, M. E.; Tarasenko, I. I.; Tolstoy, Peter M.; Neelov, Igor M.; Lähderanta, E.

doi:10.1039/c9ra02461a

Cited by 24 publications

(37 citation statements)

References 47 publications

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“…Computer simulation of peptide dendrimers was performed earlier by Brownian dynamics [59], molecular dynamics [60,61] methods, and by a numerical self-consistent field approach [62]. Synthesis and NMR study of some new peptide dendrimers with internally inserted amino acid spacers between each pair of branching points were also described in recent papers [63][64][65][66].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Structure and Local Dynamics of Two Peptide Dendrimers with the Same Backbone but with Different Side Groups in Their Spacers

et al. 2020

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In this paper, we perform computer simulation of two lysine-based dendrimers with Lys-2Lys and Lys-2Gly repeating units. These dendrimers were recently studied experimentally by NMR (Sci. Reports, 2018, 8, 8916) and tested as carriers for gene delivery (Bioorg. Chem., 2020, 95, 103504). Simulation was performed by molecular dynamics method in a wide range of temperatures. We have shown that the Lys-2Lys dendrimer has a larger size but smaller fluctuations as well as lower internal density in comparison with the Lys-2Gly dendrimer. The Lys-2Lys dendrimer has larger charge but counterions form more ion pairs with its NH 3 + groups and reduce the bare charge and zeta potential of the first dendrimer more strongly. It was demonstrated that these differences between dendrimers are due to the lower flexibility and the larger charge (+2) of each 2Lys spacers in comparison with 2Gly ones. The terminal CH 2 groups in both dendrimers move faster than the inner CH 2 groups. The calculated temperature dependencies of the spin-lattice relaxation times of these groups for both dendrimers are in a good agreement with the experimental results obtained by NMR.

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Section: Introductionmentioning

confidence: 99%

Comparison of Structure and Local Dynamics of Two Peptide Dendrimers with the Same Backbone but with Different Side Groups in Their Spacers

et al. 2020

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“…Both lysine and arginine are charged aliphatic amino acids with amino groups that are protonated under biological conditions, which may ensure the efficient delivery of nucleic acid into the cells and its endosomal escape. It has been shown that the insertion of Arg residues between inner Lys branching points made the dendrimer's interior more charged and thus more hydrophilic [34]. What is more, a guanidine moiety of Arg shows high affinity for phosphate groups of DNA, increasing its condensation.…”

Section: Resultsmentioning

confidence: 99%

“…In light of these results, it seemed reasonable to continue the research on the use of PLL dendrimers as carriers for other types of genetic material. Substitution of lysine residues with different amino acids may bring several benefits to PLL dendrimers considered as a system for gene delivery, changing their flexibility and distribution of charged groups, providing additional interactions with nucleic acids, and affecting cellular uptake levels [24,[33][34][35]. Both lysine and arginine are charged aliphatic amino acids with amino groups that are protonated under biological conditions, which may ensure the efficient delivery of nucleic acid into the cells and its endosomal escape.…”

Section: Resultsmentioning

confidence: 99%

“…PLL dendrimers of the 3rd generation (D3): D3K2 (containing two additional lysine residues (Lys-Lys) between each pair of neighboring branching points of standard lysine dendrimer of the 3rd generation), D3R2 and D3H2 (with two additional arginine (Arg-Arg), or histidine (His-His) residues, respectively, between the same branching points) ( Figure 1) were synthesized, purified, and characterized as described previously [33][34][35].…”

Section: Dendrimersmentioning

confidence: 99%

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Poly(lysine) Dendrimers Form Complexes with siRNA and Provide Its Efficient Uptake by Myeloid Cells: Model Studies for Therapeutic Nucleic Acid Delivery

Gorzkiewicz

Kopeć

Janaszewska

et al. 2020

IJMS

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The disruption of the cellular pathways of protein biosynthesis through the mechanism of RNA interference has been recognized as a tool of great diagnostic and therapeutic significance. However, in order to fully exploit the potential of this phenomenon, efficient and safe carriers capable of overcoming extra- and intracellular barriers and delivering siRNA to the target cells are needed. Recently, attention has focused on the possibility of the application of multifunctional nanoparticles, dendrimers, as potential delivery devices for siRNA. The aim of the present work was to evaluate the formation of dendriplexes using novel poly(lysine) dendrimers (containing lysine and arginine or histidine residues in their structure), and to verify the hypothesis that the use of these polymers may allow an efficient method of siRNA transfer into the cells in vitro to be obtained. The fluorescence polarization studies, as well as zeta potential and hydrodynamic diameter measurements were used to characterize the dendrimer:siRNA complexes. The cytotoxicity of dendrimers and dendriplexes was evaluated with the resazurin-based assay. Using the flow cytometry technique, the efficiency of siRNA transport to the myeloid cells was determined. This approach allowed us to determine the properties and optimal molar ratios of dendrimer:siRNA complexes, as well as to demonstrate that poly(lysine) dendrimers may serve as efficient carriers of genetic material, being much more effective than the commercially available transfection agent Lipofectamine 2000. This outcome provides the basis for further research on the application of poly(lysine) dendrimers as carriers for nucleic acids in the field of gene therapy.

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“…Here, we have synthesized and deuterated a second generation lysine-based dendrimer by inserting two histidine amino acid residues into every inner segment (Figure 1). By analogy with our previous works [39,40], we have modified a dendrimer interior. The insertion of arginine or histidine amino acid residues into inner segments of lysine dendrimer could enhance its potential for drug and gene delivery (see, for instance, a recent review [19]).…”

Section: Introductionmentioning

confidence: 99%

Stable Deuterium Labeling of Histidine-Rich Lysine-Based Dendrimers

et al. 2019

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Peptide dendrimers, due to their biocompatibility and low toxicity, are highly promising candidates as nanocarriers for drugs and genes. The development of this kind of delivery system requires reliable monitoring of their metabolic and biological pathways. In this respect, hydrogen isotope labeling has tremendous importance, being a safe tool for detection of the labeled nanocarriers. In this work, we have synthesized new histidine-rich lysine-based dendrimers (Lys-2His dendrimer) with two linear histidine (His) residues in every inner segment. The presence of His residues has enabled us to perform controlled deuteration of Lys-2His dendrimers. The high deuteration degree (around 70%) does not practically change after redissolving the samples in H2O and heating them at 40 °C, which indicates the isotopic label stability.

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Lysine-based dendrimer with double arginine residues

Abstract: A new poly-l-lysine dendrimer with arginine residues was synthesized and its structure and physical–chemical properties were analyzed by NMR spectroscopy.

Cited by 24 publications

References 47 publications

Comparison of Structure and Local Dynamics of Two Peptide Dendrimers with the Same Backbone but with Different Side Groups in Their Spacers

Comparison of Structure and Local Dynamics of Two Peptide Dendrimers with the Same Backbone but with Different Side Groups in Their Spacers

Poly(lysine) Dendrimers Form Complexes with siRNA and Provide Its Efficient Uptake by Myeloid Cells: Model Studies for Therapeutic Nucleic Acid Delivery

Stable Deuterium Labeling of Histidine-Rich Lysine-Based Dendrimers

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