NMR Studies of Two Lysine Based Dendrimers with Insertion of Similar Histidine-Arginine and Arginine-Histidine Spacers Having Different Properties for Application in Drug Delivery

Autor: Nadezhda N. Sheveleva, Irina I. Tarasenko, Mikhail A. Vovk, Mariya E. Mikhailova, Igor M. Neelov, Denis A. Markelov
Rok vydání: 2023
Předmět:
Zdroj: International Journal of Molecular Sciences; Volume 24; Issue 2; Pages: 949
ISSN: 1422-0067
Popis: In this paper we study two lysine-based peptide dendrimers with Lys-His-Arg and Lys-Arg-His repeating units and terminal lysine groups. Combination of His and Arg properties in a dendrimer could be important for biomedical applications, especially for prevention of dendrimer aggregation and for penetration of dendrimers through various cell membranes. We describe the synthesis of these dendrimers and the confirmation of their structure using 1D and 2D Nuclear Magnetic Resonance (NMR) spectroscopy. NMR spectroscopy and relaxation are used to study the structural and dynamic properties of these macromolecules and to compare them with properties of previously studied dendrimers with Lys-2Arg and Lys-2His repeating units. Our results demonstrate that both Lys-His-Arg and Lys-Arg-His dendrimers have pH sensitive conformation and dynamics. However, properties of Lys-His-Arg at normal pH are more similar to those of the more hydrophobic Lys-2His dendrimer, which has tendency towards aggregation, while the Lys-Arg-His dendrimer is more hydrophilic. Thus, the conformation with the same amino acid composition of Lys-His-Arg is more pH sensitive than Lys-Arg-His, while the presence of Arg groups undoubtedly increases its hydrophilicity compared to Lys-2His. Hence, the Lys-His-Arg dendrimer could be a more suitable (in comparison with Lys-2His and Lys-Arg-His) candidate as a pH sensitive nanocontainer for drug delivery.
Databáze: OpenAIRE
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