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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 (Autor)

Previo

Lectura de prueba, PDF (790 KB)
Indice, PDF (540 KB)

ISBN-13 (Impresion) 9783736999961
ISBN-13 (E-Book) 9783736989962
Idioma Inglés
Numero de paginas 182
Laminacion de la cubierta Brillante
Edicion 1.
Lugar de publicacion Göttingen
Lugar de la disertacion Karlsruhe
Fecha de publicacion 09.04.2019
Clasificacion simple Tesis doctoral
Area Química
Química orgánica
Bioquímica, biología molecular, tecnología genética
Palabras claves 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
Descripcion

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.