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. 2019 Jul 6;24(13):2481.
doi: 10.3390/molecules24132481.

Stable Deuterium Labeling of Histidine-Rich Lysine-Based Dendrimers

Nadezhda N Sheveleva  1 , Denis A Markelov  2 , Mikhail A Vovk  1 , Irina I Tarasenko  3 , Mariya E Mikhailova  1 , Maxim Yu Ilyash  4 , Igor M Neelov  4 , Erkki Lahderanta  5
Affiliations

Stable Deuterium Labeling of Histidine-Rich Lysine-Based Dendrimers

Nadezhda N Sheveleva et al. Molecules. .

Abstract

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.

Keywords: deuterium labeling; histidine; peptide dendrimer.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Structural formula of Lis-2His dendrimer. Green color marks the core, black corresponds to the main chain, violet marks the side segments, and red corresponds to the terminal segments.
Figure 2
Figure 2
1H NMR spectrum of Lis-2His dendrimer in D2O at 25 °C.
Figure 3
Figure 3
13C NMR spectrum of Lis-2His dendrimer in D2O at 25 °C. The letter symbols correspond to the designations of the groups in Figure 2.
Figure 4
Figure 4
(a) 1H and (b) 2H NMR spectra of Lys-2His dendrimer in D2O after heating. 2H NMR spectrum was recorded using a pulse sequence that suppresses the solvent signal. The letter symbols correspond to the designations of the groups in Figure 2.
Figure 5
Figure 5
The temperature dependence of the concentration of protons at the C2 carbons of histidine imidazole rings (8.12 ppm) during heating.
Figure 6
Figure 6
Evolution of the peak at 8.12 ppm from protons at the C2 carbons of the imidazole rings of histidine residues in Lys-2His dendrimer: (a) 1H NMR spectra of Lys-2His dendrimer in D2O before (blue) and after (red) heating; (b) 1H NMR spectra of Lys-2His dendrimer in H2O before (red) and after (green) heating. The peaks from protons in the NH groups are indicated by *.
See this image and copyright information in PMC

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