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, T_1H, of two similar peptide dendrimers of the second generation, with and without side fragments in their inner segments. Temperature dependences of 1/T_1H 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/T_1H 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/T_1H temperature dependences of terminal groups which are similar for both dendrimers.

Figure 1

Schematic structures of the second generation (a) Lys-2Gly and (b) Lys-2Lys dendrimers. The colors mark following dendrimer parts: cores (green), inner segments of main chains (black), side fragments (blue), terminal segments (red). Red solid circles are the branching points.

Figure 2

Chemical structures of inner and terminal segments in the Lys-2Gly and Lys-2Lys dendrimers. Lys-2Gly inner segments containing (a) ε-part and (b) α-part of lysine and two glycine residues; Lys-2Lys inner segments containing (c) ε-part and (d) α-part of lysine and two lysine residues; and (e) the terminal segment is the same for both dendrimers. Black color marks the main chain, blue one corresponds to the side fragments. Red open circles show the branching points. NMR active methylene groups of the main chain connected with NH groups are highlighted in orange color and CH₂ groups connected with protonated NH₃⁺ groups are highlighted in magenta color.

Figure 3

¹Н NMR spectra of the Lys-2Lys (a), Lys-2Gly (b) and Lys (c) G2 dendrimers at T = 293 K. Peak 1 corresponds to inner СН₂-(NH) and peak 2 to terminal CH₂-(NH₃⁺) groups.

Figure 4

Temperature dependence of the spin-lattice relaxation rate, 1/T_1H, of inner СН₂-(NH) groups and terminal CH₂-(NH₃⁺) groups.