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SUMMARY:Unlocking Chemistry:  Pushing the Limits of Bioorthogonal Click-To
 -Release
DTSTART:20260224T161500
DTEND:20260224T171500
DTSTAMP:20260416T131755Z
UID:108cf2cca8a221762bc64d91f44558d757b9c3625b6ee14d082d195c
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof. Hannes Mikula\nTU Wien\, Austria\nBioorthogonal chemistr
 y provides powerful tools for selective ligation and bond-cleavage in comp
 lex biological environments. Among these\, the tetrazine/trans-cyclooctene
  (Tz/TCO) click-to-release reaction enables controlled molecular disassemb
 ly\, advancing targeted drug delivery and prodrug activation\, with first 
 clinical trials now underway. However\, conventional Tz/TCO systems suffer
 ed from incomplete or slow click-to-release.1 We developed next-level mole
 cular tools with exceptional kinetics and precision: a C2-symmetric TCO (C
 2TCO) that enables near-instantaneous cleavage\,2 hydroxypyridyl-tetrazine
 s that achieve complete and accelerated release\,3 and the intramolecularl
 y controlled iTCO that allows highly reactive tetrazines to function as ef
 ficient molecular scissors\, elevating click-to-release chemistry to the p
 erformance level required for efficient in vivo application.4 Together\, t
 hese tools enable fast and near-quantitative bond-cleavage and cascade rea
 ctions with molecular precision for bioorthogonal ON/OFF control. This pre
 sentation will highlight the molecular designs and mechanistic insights th
 at led us to redefine the performance limits of Tz/TCO click-to-release ch
 emistry.\n\nReferences\n[1] Keppel P.\; Hecko S.\; Mikula H.\, Top. Curr. 
 Chem. 2025\, 383\, 25.\n[2] Wilkovitsch M.\; Haider M.\; Sohr B.\; Herrman
 n B.\; Klubnick J.\; Weissleder R.\; Carlson J. C. T.\; Mikula H.\, J. Am
 . Chem. Soc. 2020\, 142\, 19132-19141.\n[3] Wilkovitsch M.\; Kuba W.\; Kep
 pel P.\; Sohr B.\; Löffler A.\; Kronister S.\; Fernandez del Castillo A.\
 ; Goldeck M.\; Dzijak R.\; Rahm M.\; Vrabel M.\; Svatunek D.\; Carlson J. 
 C. T.\; Mikula H.\, Angew. Chem. Int. Ed. 2025\, 64\, e202411707.\n[4] Kub
 a W.\; Schiefer A.\; Löffler A.\; Houszka N.\; Schnöll S.\; Staudt M.\; 
 Demuth T.\; Sohr B.\; Haider M.\; Kohler R.\; Weissleder R.\; Svatunek D.\
 ; Carlson J. C. T.\; Mikula H.\, ChemRxiv 2025\, DOI: 10.26434/chemrxiv-20
 25-7s39f.\n\n 
LOCATION:BCH 2201 https://plan.epfl.ch/?room==BCH%202201
STATUS:CONFIRMED
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