High-throughput screening and evaluation of combinatorial cell penetrating peptoid libraries to identify organelle- and organ-specific drug delivery molecules

Beschreibung

Drug delivery systems can increase the pharmacokinetic and pharmacodynamic properties of various therapeutic agents. These systems can ensure a controlled release, improve the specificity of drugs to the target tissue, and therefore decrease side effects to the healthy surrounding tissue. In this work cell penetrating peptoids, which mimic the structure of peptides but exhibit increased stability, were investigated as organelle- and organ-specific carrier molecules. Several fluorescently labelled peptoid libraries, differing for example in length and side-chain composition, were synthesized and investigated with high-throughput screenings in different cell lines. The focus was on the elucidation of structure-function relationships for cellular uptake, intracellular localization and cytotoxicity. Furthermore, the organ targeting of the peptoids was analysed in in vivo studies by using zebrafish as model organism. In addition, the influence of the fluorescent dye on the localization and uptake of the peptoids was investigated.

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Ilona Diana Majella Wehl

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Lipinski chemical biology combinatorial synthesis cytotoxicity drug delivery drug delivery fluorescence fluorescent dye high-throughput screening imaging organ-specific peptoids spheroids structure-function relationship zebrafish

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