Ethynyl benziodoxolones: functional terminators for cell-penetrating poly(disulfide)s

Article Article scientifique Article Ethynyl benziodoxolones: functional terminators for cell-penetrating poly(disulfide)s eng 2016 author Morelli Paola 816461 author Martin Benlloch Xavier 835218 author Tessier Romain author Waser Jérôme author Sakai Naomi 0000-0002-9460-1944 131140 author Matile Stefan 0000-0002-8537-8349 129654 3465-3470 10.1039/C6PY00562D 1759-9954 http://xlink.rsc.org/?DOI=C6PY00562D Outperforming cell-penetrating peptides (CPPs), cell-penetrating poly(disulfide)s (CPDs) are attracting increasing interest. CPDs are accessible by ring-opening disulfide-exchange polymerization under mild conditions in neutral water. Initiation of the polymerization with thiols results in quantitative labeling of one CPD terminus with initiators of free choice. In contrast, labeling of the other terminus with iodoacetamides has so far been ineffective because of poor yields and the high excess of reagents needed. In this report, we introduce hypervalent iodine reagents as operational terminators of the synthesis of CPDs, also at high dilution. The power of the approach is exemplified with green-fluorescent initiators and ethynyl benziodoxolone terminators containing additional azides for CuAAC with red-fluorescent alkynes. The absorption spectra of the resulting CPDs demonstrate that stoichiometric application of ethynyl benziodoxolone terminators results in 46% incorporation. FRET between green-fluorescent initiators and red-fluorescent terminators demonstrates significant folding of CPDs in solution; it disappears upon reductive depolymerization. Substrates attached to the new termini are shown to enter into HeLa cells. Moreover, disappearance of FRET in the cytosol corroborated the reductive cleavage of CPDs upon internalization. Beyond the introduction of enthynyl benziodoxolones as operational terminators, these findings thus demonstrate also the compatibility of CuAAC with poly(disulfide)s and the usefulness of doubly-labeled CPDs for structural and mechanistic studies. Dewey 540 36 Département de chimie organique 141 false 761 Groupe Matile Polymer chemistry 7 20 7fe0a47e-f5a9-4700-b546-552885cda6f8 Article (Published version) Restricted c6py00562d.pdf 2771961 application/pdf restrictedAccess Faculté des sciences / Section de chimie et biochimie / Département de chimie organique

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Ethynyl benziodoxolones: functional terminators for cell-penetrating poly(disulfide)s	Polymer chemistry			2016	623	1

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Martin Benlloch, Xavier