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.
Subject(s)
Dendrimers , Histidine , Histidine/chemistry , Lysine/chemistry , Dendrimers/chemistry , Arginine , Amino AcidsABSTRACT
The ability of aminoethyl methacrylate cationic copolymers to stabilize silver nanoparticles in water was investigated. Sodium borohydride (NaBH4) was employed as a reducing agent for the preparation of silver nanoparticles. The objects were studied by ultraviolet-visible (UV-vis) spectroscopy, dynamic light scattering (DLS), analytical ultracentrifugation (AUC) and scanning electron microscopy (SEM). Formation of nanoparticles in different conditions was investigated by varying ratios between components (silver salt, reducing agent and polymer) and molar masses of copolymers. As a result, we were successful in obtaining nanoparticles with a relatively narrow size distribution that were stable for more than six months. Consistent information on nanoparticle size was obtained. The holding capacity of the copolymer was studied.
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.
Subject(s)
Dendrimers/chemistry , Deuterium/chemistry , Histidine/chemistry , Isotope Labeling , Lysine/chemistry , Hydrogen/chemistry , Molecular Structure , Nuclear Magnetic Resonance, BiomolecularABSTRACT
Due to their well-defined structure, multivalency, biocompatibility, and low toxicity, lysine dendrimers can be used as safe and efficient nanocarriers for drug and gene delivery. One useful strategy for improving the gene delivery properties of dendrimers is modification with arginine amino acid (Arg) residues. Incorporation of Arg residues could be favorable for the enhancement in transfection efficiency of lysine based dendrimers. In this work, we have synthesized a new second-generation poly-l-lysine dendrimer with repeating units containing two linear Arg residues between neighboring lysine branching points (Lys-2Arg dendrimer) and studied its physicochemical properties. We confirmed the structure of Lys-2Arg dendrimer using various one- and two-dimensional 1H and 13C NMR spectroscopy methods. Comparison of T 1H relaxation data for Lys-2Arg and Lys-2Lys dendrimers showed that the replacement of double Lys residues with double Arg residues resulted in a sharp decrease in the mobility of methylene groups in side segments and in the main chain of ε-Lys inner segments. We suggest that this unexpected effect is caused by a guanidine-guanidine pairing effect in water, which leads to entanglements between dendrimer branches.