TY - JOUR
T1 - A Chalcogen-Bonding Cascade Switch for Planarizable Push–Pull Probes
AU - Macchione, Mariano
AU - Goujon, Antoine
AU - Strakova, Karolina
AU - Humeniuk, Heorhii V.
AU - Licari, Giuseppe
AU - Tajkhorshid, Emad
AU - Sakai, Naomi
AU - Matile, Stefan
N1 - Funding Information:
We thank Aurelien Roux and Adai Colom for assistance, Christian Eggeling for advice, the NMR, the MS, and the bioimaging platforms for services, and the University of Geneva, the Swiss National Centre of Competence in Research (NCCR) Chemical Biology, the NCCR Molecular Systems Engineering, and the Swiss NSF for financial support. Computational component of the project has been supported by the National Institutes of Health grant P41-GM104601 to E.T. All the simulations were performed using resources provided by NCSA Blue Waters and XSEDE allocations to E.T. (grant MCA06N060).
Publisher Copyright:
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/10/28
Y1 - 2019/10/28
N2 - Planarizable push–pull probes have been introduced to demonstrate physical forces in biology. However, the donors and acceptors needed to polarize mechanically planarized probes are incompatible with their twisted resting state. The objective of this study was to overcome this “flipper dilemma” with chalcogen-bonding cascade switches that turn on donors and acceptors only in response to mechanical planarization of the probe. This concept is explored by molecular dynamics simulations as well as chemical double-mutant cycle analysis. Cascade switched flipper probes turn out to excel with chemical stability, red shifts adding up to high significance, and focused mechanosensitivity. Most important, however, is the introduction of a new, general and fundamental concept that operates with non-trivial supramolecular chemistry, solves an important practical problem and opens a wide chemical space.
AB - Planarizable push–pull probes have been introduced to demonstrate physical forces in biology. However, the donors and acceptors needed to polarize mechanically planarized probes are incompatible with their twisted resting state. The objective of this study was to overcome this “flipper dilemma” with chalcogen-bonding cascade switches that turn on donors and acceptors only in response to mechanical planarization of the probe. This concept is explored by molecular dynamics simulations as well as chemical double-mutant cycle analysis. Cascade switched flipper probes turn out to excel with chemical stability, red shifts adding up to high significance, and focused mechanosensitivity. Most important, however, is the introduction of a new, general and fundamental concept that operates with non-trivial supramolecular chemistry, solves an important practical problem and opens a wide chemical space.
KW - chalcogen bonds
KW - fluorescent probes
KW - force imaging
KW - lipid bilayer membranes
KW - push-pull fluorophores
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U2 - 10.1002/anie.201909741
DO - 10.1002/anie.201909741
M3 - Article
C2 - 31539191
AN - SCOPUS:85073610447
SN - 1433-7851
VL - 58
SP - 15752
EP - 15756
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 44
ER -