In-silico design of peptide-based transfection systems, in-vitro validation, and up-take pathways investigation.
2017 (English)Licentiate thesis, comprehensive summary (Other academic)
Cell-penetrating peptide-based transfection systems (PBTS) are a promising group of drug delivery vectors. Cell-penetrating peptides (CPPs) are short cationic peptides that are able of transporting cell non-permeant cargos into different cell types. Some CPPs can be used to form non-covalent complexes with oligonucleotides for gene delivery applications. For the potential use of CPPs as drug delivery tools, it is important to understand the mechanism of uptake. Here, a fragment quantitative structure–activity relationships (FQSAR) model is generated to predict novel peptides based on approved alpha helical conformers and assisted model construction with energy refinement molecular mechanics simulations of former peptides. The modeled peptides were examined for plasmid transfection efficiency and compared with their predicted biological activity. The best predicted peptides were efficient for plasmid transfection with significant enhancement compared to the former group of peptides. Our results confirm that FQSAR model refinement is an efficient method for optimizing PBTS for improved biological activity. Additionally, using RNA sequencing, we demonstrated the involvement of autophagy pathways in PBTS uptake.
Place, publisher, year, edition, pages
Department of Neurochemistry, Stockholm University , 2017. , 50 p.
Cell-penetrating peptides, QSAR, PepFect
Chemical Sciences Biochemistry and Molecular Biology
Research subject Neurochemistry with Molecular Neurobiology
IdentifiersURN: urn:nbn:se:su:diva-140139OAI: oai:DiVA.org:su-140139DiVA: diva2:1077720
2017-03-15, Heilbronnsalen, C458, Svante Arrhenius väg 16B, Stockholm, 14:00 (English)
Nilsson, IngMarie, Docent
Langel, Ülo, Professor
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