Planta Med 2019; 85(06): 513-518
DOI: 10.1055/a-0863-4795
Natural Product Chemistry and Analytical Studies
Rapid Communications
Georg Thieme Verlag KG Stuttgart · New York

Structure-Activity Relationship of Transfection-Modulating Saponins – A Pursuit for the Optimal Gene Trafficker

Simko Sama
1   Institut für Pharmazie, Freie Universität Berlin, Berlin, Germany
,
Gerold Jerz
2   Institut für Lebensmittelchemie, Technische Universität Braunschweig, Braunschweig, Germany
,
Mayank Thakur
3   Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Charité Campus Virchow, Berlin, Germany
,
Matthias F. Melzig
1   Institut für Pharmazie, Freie Universität Berlin, Berlin, Germany
,
Alexander Weng
1   Institut für Pharmazie, Freie Universität Berlin, Berlin, Germany
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 21. November 2018
revised 06. Februar 2019

accepted 17. Februar 2019

Publikationsdatum:
01. März 2019 (online)


Abstract

The ability of certain triterpenoid saponins to modulate the endosomal release during the process of endocytosis and to ensure a nontoxic and efficient transfection recently led to an exceptional interest in the field of nonviral gene delivery. In vitro and in vivo studies demonstrated promising results in terms of tumor growth inhibition after the delivery of a suicide gene such as saporin and dianthin. With that, the question arises which structural features are necessary or advantageous to achieve an effective endosomal escape. Former studies described certain important characteristics a potent saponin should have. Particularly SA1641 (Gypsophila paniculata) and SO1861 (Saponaria officinalis) played an utmost important role to get a first insight into the structure-activity relationship. However, a number of issues such as the purpose of functional groups on the aglycon and the substitution of sugars and their modification remain unsolved and their value needs to be specified. By conducting a screening of several diverse saponins in terms of their transfection improving ability, we aimed to examine these questions in more detail and get a better understanding of the relevant features. The transfection of Neuro-2A-cells with GFP-DNA containing peptide-based nanoplexes provided a reliable method in order to compare the activity of the saponins. With that, we were able to provide new and essential insights regarding the structure-activity relationship of transfection-modulating saponins and give an idea of how a highly potent saponin for future gene therapies may look like.

 
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