111586-92-6Relevant articles and documents
Synthesis of an enlarged library of dynamic DNA activators with oxime, disulfide and hydrazone bridges
Montenegro, Javier,Bang, Eun-Kyoung,Sakai, Naomi,Matile, Stefan
, p. 10436 - 10443 (2012/10/18)
Dynamic amphiphiles have a bridge between their charged head and their hydrophobic tails. The presence of dynamic covalent bonds is of interest for differential and biosensing applications as well as for rapid access to the libraries needed to screen for gene delivery or cellular uptake of siRNA. However, efforts to develop libraries have so far concentrated on hydrazone bridges to monocationic heads. Here, we report synthesis efforts to enlarge this focused library with oxime and disulfide bridges and dynamic amphiphiles with more than one positive charge. Evaluation in fluorogenic vesicles reveals best activation of DNA as ion transporters by dynamic amphiphiles with dendritic scaffolds, doubly charged heads and four tails. Moreover, oximes, contrary to hydrazones, remain active under acidic conditions. Linear elongation of dendritic head-groups seems to cause increasing detergent effects and should therefore be avoided. Head on: Design, synthesis and evaluation of dynamic amphiphiles with singly or doubly charged peptide dendrons as head-groups; hydrazones, oximes and disulfides as bridges; and with fragrant tails are reported. Amphiphiles with two charges and four tails (see figure) are identified as the most powerful activators of DNA as ion transporters and thus as the most promising family to screen for gene and siRNA delivery. Copyright
