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Microgels as carriers of antimicrobial peptides – Effects of peptide PEGylation

Nordstr̦m, R and Nystr̦m, L and Ilyas, H and Atreya, HS and Borro, BC and Bhunia, A and Malmsten, M (2019) Microgels as carriers of antimicrobial peptides РEffects of peptide PEGylation. In: Colloids and Surfaces A: Physicochemical and Engineering Aspects, 565 . pp. 8-15.

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Official URL: https://doi.org/10.1016/j.colsurfa.2018.12.049


Delivery systems are likely to be central for the translation of antimicrobial peptides (AMPs) towards therapeutics. Addressing AMP interactions with microgel carriers, we here investigate how poly(ethylene glycol) conjugation (‘PEGylation’) of AMPs affect their loading and release to/from microgels, combining structural studies using nuclear magnetic resonance (NMR) with ellipsometry, circular dichroism spectroscopy (CD), and light scattering. Such studies demonstrate that poly(ethyl acrylate-co-methacrylic acid) microgels bind considerable amounts of the positively charged AMP KYE28 (KYEITTIHNLFRKLTHRLFRRNFGYTLR) and its PEGylated variants KYE28-PEG48, PEG48-KYE28, and PEG24-KYE28-PEG24. Z-potential measurements indicate that KYE28 resides primarily inside the microgel core, and that localization of the PEGylated peptides is shifted towards the microgel corona. Furthermore, while all peptides are disordered in solution, CD measurements report on helix induction on microgel binding, particularly so for the PEGylated peptides. Addressing such conformational changes in more detail, NMR structural studies showed that peptide-microgel interactions are facilitated by a hydrophobic domain formed by the peptide after microgel binding, and with modulating electrostatic/salt bridge interaction between the positively charged peptide residues and negative microgel charges. As the microgels remain negatively charged also at high peptide load, membrane disruption and antimicrobial effects necessitates peptide release, demonstrated to be promoted by PEGylation and high ionic strength. Importantly, microgel loading, as well as peptide localization, conformation, and release, did not depend significantly on PEG conjugation site, but instead seems to be dictated by the PEG content of the peptide conjugates.

Item Type: Journal Article
Publication: Colloids and Surfaces A: Physicochemical and Engineering Aspects
Publisher: Elsevier B.V.
Additional Information: The copyright for this article belongs to Elsevier B.V.
Keywords: Circular dichroism spectroscopy; Controlled drug delivery; Dichroism; Drug delivery; Ionic strength; Light scattering; Microorganisms; Nuclear magnetic resonance; Nuclear magnetic resonance spectroscopy; Polyethylene glycols; Targeted drug delivery, Anti-microbial effects; Antimicrobial peptide; Conformational change; High ionic strength; Microgel; Nuclear Magnetic Resonance (NMR); PEgylation; Positively charged peptides, Peptides, drug carrier; macrogol; peptide; polypeptide antibiotic agent, amino terminal sequence; Article; carboxy terminal sequence; circular dichroism; comparative study; conformational transition; conjugation; electric potential; ellipsometry; epitope mapping; gel; light scattering; nuclear magnetic resonance; nuclear magnetic resonance spectroscopy; nuclear Overhauser effect; PEGylation; priority journal; protein conformation; surface property; zeta potential
Department/Centre: Division of Chemical Sciences > NMR Research Centre (Formerly Sophisticated Instruments Facility)
Date Deposited: 16 Dec 2022 07:46
Last Modified: 16 Dec 2022 07:46
URI: https://eprints.iisc.ac.in/id/eprint/78366

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