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A Systematic Structure-Activity Study of a New Type of Small Peptidic Transfection Vector Reveals the Importance of a Special Oxo-Anion-Binding Motif for Gene Delivery.
Junghänel, Sandra; Karczewski, Sarah; Bäcker, Sandra; Knauer, Shirley K; Schmuck, Carsten.
Afiliación
  • Junghänel S; Institute of Organic Chemistry, University of Duisburg-Essen, Universitätsstrasse 7, 45117, Essen, Germany.
  • Karczewski S; Institute of Molecular Biology, University of Duisburg-Essen, Universitätsstrasse 7, 45117, Essen, Germany.
  • Bäcker S; Institute of Molecular Biology, University of Duisburg-Essen, Universitätsstrasse 7, 45117, Essen, Germany.
  • Knauer SK; Institute of Molecular Biology, University of Duisburg-Essen, Universitätsstrasse 7, 45117, Essen, Germany.
  • Schmuck C; Institute of Organic Chemistry, University of Duisburg-Essen, Universitätsstrasse 7, 45117, Essen, Germany.
Chembiochem ; 18(22): 2268-2279, 2017 11 16.
Article en En | MEDLINE | ID: mdl-28914486
We discovered a new class of artificial peptidic transfection vectors based on an artificial anion-binding motif, the guanidiniocarbonylpyrrole (GCP) cation. This new type of vector is surprisingly smaller than traditional systems, and our previous work suggested that the GCP group was important for promoting critical endosomal escape. We now present here a systematic comparison of similar DNA ligands featuring our GCP oxo-anion-binding motif with DNA ligands only consisting of naturally occurring amino acids. Structure-activity studies showed that the artificial binding motif clearly outperformed natural amino acids such as histidine, lysine, and arginine. It improved the ability to shuttle foreign genetic material into cells, yet successfully mediated endosomal escape. Also, plasmids that were complexed by our artificial ligands were stabilized against cytosolic degradation to some extent. This resulted in the successful expression of plasmid information (comparable to gold standards such as polyethyleneimine). Hence, our study clearly demonstrates the importance of the tailor-made GCP anion-binding site for efficient gene transfection.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Pirroles / Transfección / Guanidina / Genes Límite: Humans Idioma: En Revista: Chembiochem Asunto de la revista: BIOQUIMICA Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Pirroles / Transfección / Guanidina / Genes Límite: Humans Idioma: En Revista: Chembiochem Asunto de la revista: BIOQUIMICA Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania