Exploring the physicochemical and morphological properties of peptide‐hybridized dendrimers (DendriPeps) and their aggregates

Abstract

This article presents an integrated experimental and computational study of DendriPeps, a novel class of dendrimers featuring a polyamidoamine (PAMAM) backbone hybridized with peptide segments. Hydroxyl‐terminated Generation 2 (G.2) DendriPeps, comprising either four lysines (Lys) or four glutamic acids (Glu), and G.3 DendriPeps, comprising 8 Lys or 8 Glu, were first characterized in terms of hydrodynamic radius (Rh) and ζ‐potential in aqueous solution. Unlike PAMAM dendrimers, DendriPeps form aggregates with Rh between 60 and 980 nm and ζ‐potential between −130 and 80 mV despite their strong net charge. Upon application of shear, all aggregates disassemble into monomeric DendriPeps (Rh ~ 1–3 nm), but reform rapidly as shear is removed. Rheological characterization confirmed that DendriPep aggregates are disrupted by mild shear, but reform reversibly. Molecular dynamics simulations, informed by titrimetry, suggest that DendriPep aggregation derives from their multipolar structure and ability to rearrange the intermolecular/intramolecular pairing of titratable moieties at different pH values.

Synthesis, structure, and function of internally functionalized dendrimers

“…For example, protein mimetic IFDs have been demonstrated as catalysts or antibiotics 35,36 ; we have shown that DendriPeps exhibit unusual solution phase behavior resulting in "soft" nanoparticles the formation of which is highly sensitive to shear forces. 92 While still under development, we believe this behavior may be exploited for exciting advancements in biological applications. This review highlights both hydrophilic IFDs as relevant compounds for biological applications, and lipophilic IFDs as relevant for catalysis or light harvesting.…”

“…92 Colcom, a French start-up, has commercialized a dendrimer-like structure first discovered by Collet et al and known as "lysine dendrigrafts," which display primary amine functionalities along its backbone and surface ( Figure 11). [77][78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][94][95][96][97][98][99][100][101][102][103][104][105][106][127][128][129][130][131][132][133][134][135][136][137][138] Lysine dendrigrafts are primarily utilized for drug 89 and gene delivery. 107 but have also been investigated for their potential as a coagulant, 108 imaging agent, 95 and substrates for tissue engineering.…”