Exploring the physicochemical and morphological properties of peptide-hybridized dendrimers (DendriPeps) and their aggregates |
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| Authors: | Ryan J. Smith Thomas Fabiani Siyao Wang Srivatsan Ramesh Saad Khan Erik Santiso Fernando Luis Barroso da Silva Christopher Gorman Stefano Menegatti |
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| Affiliation: | 1. Department of Chemistry, North Carolina State University, Raleigh, North Carolina, USA;2. Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina, USA;3. Faculty of Pharmaceutical Sciences at Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil |
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| 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. |
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| Keywords: | dendrimers DendriPeps molecular dynamics PAMAM reversible aggregation |
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