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Metal and tyrocidine nano-assemblies to create broadspectrum metal-peptide formulations
Thesis (MSc)--Stellenbosch University, 2023.
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| Format: | Thesis |
| Language: | en_ZA |
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Stellenbosch : Stellenbosch University
2023
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| _version_ | 1867613968457007104 |
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| access_status_str | Open Access |
| author | De Villiers, Carmen |
| author2 | Rautenbach, Marina |
| author_browse | De Villiers, Carmen Rautenbach, Marina |
| author_facet | Rautenbach, Marina De Villiers, Carmen |
| author_sort | De Villiers, Carmen |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MSc)--Stellenbosch University, 2023. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/127255 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:44:34.165Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/127255 Metal and tyrocidine nano-assemblies to create broadspectrum metal-peptide formulations De Villiers, Carmen Rautenbach, Marina Stellenbosch University. Faculty of Science. Dept. of Biochemistry. Tyrocidines Antimicrobial peptides Metals Peptides -- Analysis Peptide antibiotics Nanostructures UCTD Thesis (MSc)--Stellenbosch University, 2023. ENGLISH ABSTRACT: Without the discovery or development of novel drugs, the phenomena of antimicrobial resistance (AMR) will continue to threaten the effective treatment of pathogenic microbes and diseases across the globe. Combinational therapies of antimicrobial peptides (AMPs) with metal nanoparticles (MNPs) have shown promise for the creation of potent nano- drugs with broad spectrum antimicrobial activity, alternative applications, and lowered risk of resistance development. In this study the combinational formulation of biologically relevant metals (magnesium, calcium, iron, copper, silver, gold, and zinc) with a group of natural antimicrobial cyclodecapeptides (CDPs) was investigated for the fabrication of potent AMP-MNP nanodrugs. The CDPs selected for this study include an aromatic residue rich peptide complex (tyrocidine mixture, Trc mix) and tryptophan rich purified analogues (tyrocidine C, TrcC and tryptocidine C, TpcC). Mass spectrophotometric studies revealed that these peptides form peptide-metal complexes with certain metals, and that the absence or presence of such complexes in formulations altered the peptides oligomerisation behaviour. Although formulations with group 11 metals lacked peptide- metal complexes, changes in peptide oligomerisation and analogue-specific prevalence was observed. Since the aromatic rich structure of these CDPs holds potential for synthesis of MNPs, it was hypothesised that the absence of peptide-metal complexes in group 11 formulations is likely due to the reduction of metal ions and formation of MNPs. This hypothesis was confirmed by spectrophotometric and spectrofluorometric studies which reported the formation of silver nanoparticles (AgNPs) in Trc mix, TpcC and TrcC formulations with silver. These studies also indicated alterations in peptide conformation when in formulation and highlighted the critical role of tryptophan for successful CDP- AgNP fabrication. Scanning transmission microscopy revealed that the peptide- synthesised spherical AgNPs were encapsulated by CDP nanostructures, a promising conjugate structure for drug delivery. Solid surface antimicrobial assays and reported additive and synergistic antimicrobial actions between CDPs and MNPs against model organisms, Gram positive Staphylococcus aureus and Gram-negative Escherichia coli, respectively. The innate self-assembly of these aromatic amino acid rich CDPs therefore holds potential to streamline the synthesis of potent yet versatile CDP-MNP nanoformulations for topical or antimicrobial surface treatments against Gram-positive and Gram-negative bacteria. Moreover, unprecedented antibacterial activity was also reported for TpcC, which could have applications in future therapies. AFRIKAANSE OPSOMMING: Sonder die ontdekking of ontwikkeling van nuwe geneesmiddels, sal die verskynsel van antimikrobiese weerstand (AMW) die effektiewe behandeling van patogene en infeksies wêreldwyd bedreig. Kombinasie-terapie met antimikrobiese peptiede (AMPs) en metaalnanopartikels (MNPs) toon belofte vir die skepping van kragtige nano- geneesmiddels met breëspektrum antimikrobiese aktiwiteit en alternatiewe toepassings met ‘n verlaagde risiko van weerstandsontwikkeling. In hierdie studie, was die kombinasie- formulering van biologies relevante metale (magnesium, kalsium, yster, koper, silwer, goud en sink) met 'n groep natuurlike antimikrobiese siklodekapeptiede (SDP'e) ondersoek vir die vervaardiging van kragtige AMP-MNP-nanogeneesmiddels. Die SDP'e wat vir hierdie studie gekies is, sluit 'n aromatiese residu-ryk peptied kompleks (tirosidien mensel, Trc mix) en triptofaan-ryk gesuiwerde analoë (tirosidien C, TrcC en triptosidien C, TpcC) in. Massaspektrofotometriese studies het onthul dat hierdie peptiede peptied- metaalkomplekse met sekere metale vorm, en dat die afwesigheid of teenwoordigheid van sulke komplekse in formulerings die peptiede-oligomeriseringsgedrag verander. Alhoewel peptied-metaalkomplekse in formulerings met groep 11-metale komplekse afwesig was, was veranderinge in peptied-oligomerisasie en analoog-spesifieke voorkoms waargeneem. Aangesien die aromaties-ryk struktuur van hierdie SDP's potensiaal skep vir sintese van MNP's, is ‘n voorgestelde hipotese dat die afwesigheid van peptied-metaal komplekse in groep 11 formulerings waarskynlik te wyte is aan die vermindering van metaalione en vorming van MNPs. Hierdie hipotese was bevestig deur spektrofotometriese en spektrofluorometriese studies wat die vorming van silwer nanopartikels (AgNPs) in Trc mix, TpcC en TrcC formulerings met silwer gerapporteer het. Hierdie studies het ook peptiedkonformasie veranderinge in formulering getoon, sowel as die kritieke rol van triptofaan in suksesvolle SDP-AgNP vervaardiging. Skandeertransmissie-mikroskopie het gewys dat die peptied-gesintetiseerde AgNP's deur SDP-nanostrukture ingekapsuleer was, 'n belowende gekonjugeerde struktuur vir geneesmiddelaflewering. Soliede- oppervlak antimikrobiese toetse het additiewe en sinergistiese antimikrobiese aksies tussen SDP's en MNP's teen model organismes, Gram-positiewe Staphylococcus aureus en Gram-negatiewe Escherichia coli, onderskeidelik gerapporteer. Die inhirente selfassosieëring van hierdie aromatiese aminosuurryke SDP's hou dus die potensiaal om die sintese van kragtige dog veelsydige SDP-MNP nanoformulerings te stroomlyn vir aktuele of antimikrobiese oppervlakbehandelings teen Gram-positiewe en Gram- negatiewe bakterieë. Boonop is ongekende antibakteriese aktiwiteit ook aangemeld vir TpcC wat dus toepassings in toekomstige terapieë kan hê. Masters 2023-03-06T09:20:17Z 2023-05-18T07:12:17Z 2023-03-06T09:20:17Z 2023-05-18T07:12:17Z 2023-03 Thesis http://hdl.handle.net/10019.1/127255 en_ZA Stellenbosch University xiv, 143 pages : illustrations(some color) application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Tyrocidines Antimicrobial peptides Metals Peptides -- Analysis Peptide antibiotics Nanostructures UCTD De Villiers, Carmen Metal and tyrocidine nano-assemblies to create broadspectrum metal-peptide formulations |
| title | Metal and tyrocidine nano-assemblies to create broadspectrum metal-peptide formulations |
| title_full | Metal and tyrocidine nano-assemblies to create broadspectrum metal-peptide formulations |
| title_fullStr | Metal and tyrocidine nano-assemblies to create broadspectrum metal-peptide formulations |
| title_full_unstemmed | Metal and tyrocidine nano-assemblies to create broadspectrum metal-peptide formulations |
| title_short | Metal and tyrocidine nano-assemblies to create broadspectrum metal-peptide formulations |
| title_sort | metal and tyrocidine nano assemblies to create broadspectrum metal peptide formulations |
| topic | Tyrocidines Antimicrobial peptides Metals Peptides -- Analysis Peptide antibiotics Nanostructures UCTD |
| url | http://hdl.handle.net/10019.1/127255 |
| work_keys_str_mv | AT devillierscarmen metalandtyrocidinenanoassembliestocreatebroadspectrummetalpeptideformulations |