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dc.contributor.advisorBradley, Mark
dc.contributor.advisorLusby, Paul
dc.contributor.authorEscher, Geraldine
dc.date.accessioned2015-12-23T10:35:29Z
dc.date.available2015-12-23T10:35:29Z
dc.date.issued2013-06-29
dc.identifier.urihttp://hdl.handle.net/1842/12260
dc.description.abstractEfficient delivery into cells is essential for many applications. However, cellular access of “cell-impermeable” molecules, such as drugs, sensors, proteins and oligonucleotides, can often be severely limited due to the plasma membrane which protects cells from unregulated influx of hydrophilic materials. In order to solve this issue, several physical techniques and bio-chemical products are today available. One of them is called peptoids (N-alkylglycines). These compounds are peptidomimetics which are resistant to enzymatic degradation, non-immunogenic and are readily prepared by an Fmoc chemical approach. Peptoids based on the "TAT"-peptide (RKKRRQRRR) offer rapid cellular uptake/delivery and low cytotoxicity. In this thesis, based on previous works using fluorescein-cationic peptoids, various fluorescent N-substitued glycines (lysine-like) were prepared by the monomer method followed by solid-phase synthesis. Their cellular uptakes in vitro into several cell lines (such as HeLa, B16F10, HEK293T and primary immune cells) were examined via flow cytometry and microscopy. The cellular delivery of small molecules mediated by the 9mer polymer achieved an efficient and rapid penetration. These results open up a vast number of applications for delivery of macromolecules using nonalysine-like peptoid. In order to demonstrate this ability, the nonalysinelike carrier was used to deliver various biopolymer molecules such as peptides, GFP protein and DNA (in collaboration with Dr. Stefano Caserta). In addition, thanks to the non-cytotoxicity of this cellular transpoter (MTT assays); experiments were carried out in vivo in mice using peptoids labelled near-infrared dyes. The first results have shown that the peptoid is not toxic for the mouse and does not block cell movements. These results allowed the use of 9mer-peptoid as a cellular tracking agent. Based on the development on antimicrobial peptides, the polylysine-like peptoid was also tested as an antibiotic. Recent experiments carried out in collaboration with Dr. Kevin Dhaliwal have revealed a new antimicrobial property of the peptoids. In vitro and in vivo studies have been carried out using both gram positive and negative bacteria. These results present a promising alternative to conventional antibiotics and antimicrobial peptides (AMPs).en
dc.contributor.sponsorotheren
dc.language.isoenen
dc.publisherThe University of Edinburghen
dc.relation.hasversionDhaliwal, K., Alexander, L., Escher, G., Unciti-Broceta, A., Jansen, M., Mcdonald, N., Cardenas-Maestre, J. M., Sanchez-Martin, R., Simpson, J., Haslett, C., Bradley, M., Multi-modal molecular imaging approaches to detect primary cells in preclinical models. Faraday Discussions, 2011, 149, 107-114.en
dc.relation.hasversionDhaliwal, K., Escher, G., Unciti-Broceta, A., Mcdonald, N., Simpson, J. A., Haslett, C., Bradley, M., Far red and NIR dye-peptoid conjugates for efficient immune cell labelling and tracking in preclinical models. MedChemComm, 2011, 2, (11), 1050-1053.en
dc.subjectcellular deliveryen
dc.subjectpeptoiden
dc.subjectNIR dyeen
dc.subjectin vivoen
dc.subjectantibioticen
dc.titleCellular delivery using peptoid carriersen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


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