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

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

Ilona Diana Majella Wehl (Author)

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ISBN-13 (Hard Copy) 9783736999961
ISBN-13 (eBook) 9783736989962
Language English
Page Number 182
Lamination of Cover glossy
Edition 1.
Publication Place Göttingen
Place of Dissertation Karlsruhe
Publication Date 2019-04-09
General Categorization Dissertation
Departments Chemistry
Organic chemistry
Biochemistry, molecular biology, gene technology
Keywords combinatorial synthesis, chemical biology, peptoids, drug delivery, imaging, high-throughput screening, zebrafish, organ-specific, drug delivery, fluorescence, Lipinski, structure-function relationship, fluorescent dye, cytotoxicity, spheroids
Description

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.