I. Gabas, P. Nielsen
Nov 22, 2019
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Influential Citations
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Quality indicators
Journal
Biomacromolecules
Abstract
A series of amino- and guanidino-terminating 3- and 4-generation 2,4-diaminobutanoic acid (Dab) dendrons have been robustly synthesized on solid phase and characterized as cellular delivery agents in antisense PNA conjugates in the pLuc705 HeLa cell splice switching system. The dendron-PNA conjugates exhibited splice correction activity at one digit micromolar concentrations, and guanidino-terminating dendrons were significantly more effective than analogous amine terminating ones. Furthermore, introduction of lipophilic groups such as phenyl, alkyl or fatty acids increased efficacy, but also increased cellular toxicity. Fluorescence microscopy analyses supported an endosomal uptake mechanism and furthermore predominantly showed co-localization with late endosomes and lysosomes. The robust solid phase synthesis should make such Dab-dendrons a useful platform for further both in vitro as well as in vivo optimization.