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

Abstract

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.

Molecular Dynamics of Lysine Dendrigrafts in Methanol–Water Mixtures

“…The Bjerrum length determines when the counterion condensation occurs, so when it approaches this limit at high methanol fractions the significant changes in all electrical and conformational properties of the dendrigrafts occurs. These results are important for the use of dendrigrafts as drug and gene delivery carriers and the future construction of amphiphilic linear–dendrigraft and dendrigraft–dendrigraft block copolymer systems for drug and gene delivery [ 47 , 131 , 132 , 133 ].…”

Dendrimers: Synthesis, Encapsulation Applications and Specific Interaction with the Stratum Corneum—A Review

“…Some applications of dendrimers were already mentioned above; they derive from their physico-chemical properties, such as structural versatility, self-assembly capability, stability and ability to engage in electrostatic interactions [4][5][6][70][71][72][73]. Thus, their capacity to encapsulate molecules of appropriate size in the internal cavities or the possibility of grafting molecules covalently to their periphery allow them to be used in many fields [74].…”

“…Symmetry also plays a very important role in determining the encapsulation properties [76] since this parameter di- Various families of peptide dendrimers have also been developed in recent years [65][66][67]; these dendrimers are branched macromolecules consisting of a peptidyl core and/or peptide functional groups at the peripheries attached in a covalent manner [68]. They can be symmetrical or unsymmetrical and used as diagnostic reagents, anticancer and antiviral agents, vaccines and carriers of active principles and genes [65,69], thanks to their properties of self-assembly [67,70].…”