Light-induced antibiotic release from a coumarin-caged compound on the ultrafast timescale

Abstract

A synthesis route for puromycin caged with the photo-responsive 7-diethylaminocoumarinyl protecting group carbamate was developed. The inactivation and recovery of the cytotoxic effect of puromycin was tested with a XTT cell viability assay. The uncaging mechanism was studied by ultrafast transient absorption spectroscopy and by time-correlated single photon counting. The combination of these results with quantum-chemical calculations provided detailed insights in dynamics upon excitation. Interestingly, a change of the dipole moment due to structural rearrangements of the amino moiety led to an intermolecular charge transfer on the picosecond time-scale. IR measurements marked the successful uncaging via the release of CO, resulting from the carbamate linker. This decarboxylation constituted the rate-limiting step of the uncaging reaction and occurred on the subsecond timescale. DEACM-puromycin, thus, represents an efficient photo-activatable antibiotic for in-cell applications.

A New Photocaged Puromycin for an Efficient Labeling of Newly Translated Proteins in Living Neurons

“…Hence, application of DEACM‐puromycin prevents photodamage of the tissue. In addition, the extinction coefficient of DEACM‐puromycin is more than three times larger than the extinction coefficient of NVOC‐puromycin . Accordingly, uncaging of the coumarin caged‐compound can be induced by a less harmful light dose as compared to NVOC‐puromycin.…”

Multivalent dextran hybrids for efficient cytosolic delivery of biomolecular cargoes

“…The bathochromic shift introduced by the electron‐donating groups at the C7 position results in an absorption maximum around 390 nm. In addition, the molecule displays a high quantum yield and an ultrafast release 50–53 …”

A Coumarin Triflate Reagent Enables One‐Step Synthesis of Photo‐Caged Lipid Metabolites for Studying Cell Signaling

“…Obtaining such kinetic datasets necessitates to change the levels of cellular small molecules in a rapid fashion and to monitor downstream responses with organelle‐specific biosensors . Current methods for rapidly modulating cellular small molecules are based on optogenetic proteins, chemical dimerizers and photo‐caged or photo‐switchable chemical probes. However, implementing new optogenetic tools or chemical dimerizer systems is not straightforward and requires significant effort.…”

“…[4][5][6][7] In particular,u nderstanding fast processes such as signal transduction requires the abilityt om easure reaction kinetics in living cells. [8][9][10] Current methods for rapidlym odulating cellular small molecules are based on optogenetic proteins, [11,12] chemical dimerizers [13,14] and photo-caged [15][16][17][18][19][20][21] or photo-switchable [19,[22][23][24] chemicalp robes. [8][9][10] Current methods for rapidlym odulating cellular small molecules are based on optogenetic proteins, [11,12] chemical dimerizers [13,14] and photo-caged [15][16][17][18][19][20][21] or photo-switchable [19,[22][23][24] chemicalp robes.…”