Exploring the physicochemical and morphological properties of peptide‐hybridized dendrimers (DendriPeps) and their aggregates. Issue 16 (11th July 2020)

• Record Type: Journal Article
• Authors: Smith, Ryan J.; Fabiani, Thomas; Wang, Siyao; Ramesh, Srivatsan; Khan, Saad; Santiso, Erik; da Silva, Fernando Luis Barroso; Gorman, Christopher; Menegatti, Stefano
• Is Part Of: Journal of polymer science. Volume 58:Issue 16(2020)
• Page Start: 2234
• Page End: 2247
• Publication Date: 2020-07-11
• Subjects: dendrimers -- DendriPeps -- molecular dynamics -- PAMAM -- reversible aggregation; Polymers -- Periodicals; Polymerization -- Periodicals; Polymerization; Polymers; Periodicals; 547.7
• DOI: 10.1002/pol.20200277
• Languages: English
• ISSNs: 2642-4150

Abstract

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 ( R h ) and ζ‐potential in aqueous solution. Unlike PAMAM dendrimers, DendriPeps form aggregates with R h 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 ( R h ~ 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. Abstract : Recently developed dendrimers containing internal functional groups (DendriPeps) display striking physicochemical properties revealed through this integrated experimental and computational study. Most notably, DendriPeps form aggregates that can be disassembled and assembled upon the application and removal of shear force despite their strong net charge. 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.