New Dendrimer–Peptide Host–Guest Complexes: Towards Dendrimers as Peptide Carriers

Abstract

Adamantyl urea and adamantyl thiourea modified poly(propylene imine) dendrimers act as hosts for N-terminal tert-butoxycarbonyl (Boc)-protected peptides and form chloroform-soluble complexes. Investigations with NMR spectroscopy show that the peptide is bound to the dendrimer by ionic interactions between the dendrimer outer shell tertiary amines and the C-terminal carboxylic acid of the peptide, and also through host-urea to peptide-amide hydrogen bonding. The hydrogen-bonding nature of the peptide-dendrimer interactions was further confirmed by using Fourier transform IR spectroscopy, for which the NH- and CO-stretch signals of the peptide amide moieties shift towards lower wavenumbers upon complexation with the dendrimer. Spatial analysis of the complexes with NOESY spectroscopy generally shows close proximity of the N-terminal Boc group of the peptide to the peripheral adamantyl groups on the dendrimer host. The influence of side-chain motif on interactions with the host is analyzed by using seven different N-Boc-protected tripeptides as guests for the dendrimer. Downfield shifts of up to 1.3 ppm were observed for the guest amide NH-proton signals. These shifts decreased with increasing 'bulkiness' of the amino acid side chains. Despite this, the dendrimer was capable of making multiple peptide-dendrimer complexes when presented with a library of seven peptides. The different peptides were all present in the host, which did not show specific preferences, and could be released under mild acidic conditions. These results show the general nature of the peptide-dendrimer interactions in the formation of either single- or multiple-peptide-dendrimer complexes.

Dendrimers in Cancer Treatment and Diagnosis

“…1.1 and 1.3). Encapsulation of hydrophilic, hydrophobic, or even amphiphilic compounds as guest molecules within a dendrimer [66] can be enhanced by providing various degrees of multiple hydrogen bonding sites or ionic interactions [65,67] or highly hydrophobic interior void spaces [68,69]. A wide variety of molecules have been successfully encapsulated inside dendrimers.…”

“…A wide variety of molecules have been successfully encapsulated inside dendrimers. In early experiments, compounds used to demonstrate the ''guest molecule'' concept included easy-to-visualize dye molecules such as rose bengal [66] and Reichardt's dye [69] as well as pyridine [65] and peptides [67]. More recently, actual drugs, including 5-fluorouracil [70], 5-amino salicylic acid, pyridine, mefanminic acid and diclofenac [65], paclitaxel [71,72], docetaxel [73], as well as the anticancer agent 10-hydroxycamptothecin [69], have been successfully encapsulated.…”

New-generation biomedical materials: Peptide dendrimers and their application in biomedicine

“…Both hydrogen bond and static elec- Figure 25 (a) The interaction between the dendrimer and urea-glycine [107]. (b) The interaction between the dendrimer and Boc protected peptide [108]. tron interaction were considered to contribute to the encapsulation.…”

Host–guest chemistry of dendrimers in the gas phase

“…After an initial proton transfer from the guest acid group to the dendrimer's tertiary amines, strong electrostatic interactions exist between the acid anion of the guest molecule and bonds between the urea units of guest and host support binding. Therefore, host D enables a variety of guest molecules based on urea-acid structures to attach on its surface, even including some oligopeptides such as T (29). The most intriguing feature of such a multivalent system is the non-covalent decoration of dendrimer surface, giving rise to a dynamic binding equilibrium in solution, in which the guests can compete with each other and the guest with the optimal binding motif can easily be detected.…”