UNIGE document Scientific Article
previous document  unige:95404  next document
add to browser collection

Epidithiodiketopiperazines : strain-promoted thiol-mediated cellular uptake at the highest tension

Published in ACS Central Science. 2017, vol. 3, no. 5, p. 449-453
Abstract The disulfide dihedral angle in epidithiodiketopiperazines (ETPs) is near 0°. Application of this highest possible ring tension to strain-promoted thiol-mediated uptake results in efficient delivery to the cytosol and nucleus. Compared to the previous best asparagusic acid (AspA), ring-opening disulfide exchange with ETPs occurs more efficiently even with nonactivated thiols, and the resulting thiols exchange rapidly with nonactivated disulfides. ETP-mediated cellular uptake is more than 20 times more efficient compared to AspA, occurs without endosomal capture, depends on temperature, and is “unstoppable” by inhibitors of endocytosis and conventional thiol-mediated uptake, including siRNA against the transferrin receptor. These results suggest that ETP-mediated uptake not only maximizes delivery to the cytosol and nucleus but also opens the door to a new multitarget hopping mode of action.
Full text
Article (Published version) (2.8 MB) - public document Free access
Research groups Groupe Matile
Groupe Adibekian
(ISO format)
ZONG, Lili et al. Epidithiodiketopiperazines : strain-promoted thiol-mediated cellular uptake at the highest tension. In: ACS Central Science, 2017, vol. 3, n° 5, p. 449-453. doi: 10.1021/acscentsci.7b00080 https://archive-ouverte.unige.ch/unige:95404

310 hits



Deposited on : 2017-07-12

Export document
Format :
Citation style :