NMR studies of excluded volume interactions in peptide dendrimers

Abstract

Peptide dendrimers are good candidates for diverse biomedical applications due to their biocompatibility and low toxicity. The local orientational mobility of groups with different radial localization inside dendrimers is important characteristic for drug and gene delivery, synthesis of nanoparticles, and other specific purposes. In this paper we focus on the validation of two theoretical assumptions for dendrimers: (i) independence of NMR relaxations on excluded volume effects and (ii) similarity of mobilities of side and terminal segments of dendrimers. For this purpose we study 1H NMR spin-lattice relaxation time, T1H, of two similar peptide dendrimers of the second generation, with and without side fragments in their inner segments. Temperature dependences of 1/T1H in the temperature range from 283 to 343 K were measured for inner and terminal groups of the dendrimers dissolved in deuterated water. We have shown that the 1/T1H temperature dependences of inner groups for both dendrimers (with and without side fragments) practically coincide despite different densities of atoms inside these dendrimers. This result confirms the first theoretical assumption. The second assumption is confirmed by the 1/T1H temperature dependences of terminal groups which are similar for both dendrimers.

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

“…The mean square size for Lys-2Lys is close to 2.0 nm and for Lys2Gly it is equal 1.35 nm, thus their ratio is close to 1.5. This result is in agreement with the experimental data [63]. The variation of size of the Lys-2Lys dendrimer occurs between 1.7 nm and 2.3 nm, while the size of the Lys-2Gly dendrimer is in the range of 0.9 to 1.8 nm, i.e., the magnitudes of fluctuations are 0.6 nm and 0.9 nm, respectively.…”

“…The synthesis, NMR properties [63], and biomedical applications [57] of peptide dendrimers with Lys2Lys and Lys2Gly repeating units were published by us in recent years. These two dendrimers were chosen because they have a total positive charge large enough (+16 and +44, correspondingly) for complexation with negatively charged DNA and RNA molecules for application in gene delivery.…”

“…The experimental points [63] are depicted in these graphs too. As it can be seen from Figure 17, our results have a good agreement with the experiment.…”

“…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].…”

“…The main goal of the present paper is to investigate the structure and local orientational mobility of two peptide dendrimers having the same backbone but different volume and charge of side groups by MD method, and to compare their structural properties and orientational dynamics with the experimental results obtained earlier [63] using NMR spectroscopy. It is important to note that these dendrimers were tested as carriers for gene delivery [57].…”