Two-photon uncaging of bioactive thiols in live cells at wavelengths above 800 nm

Photoactivatable protecting groups (PPGs) are useful for a broad range of applications ranging from biology to materials science. In chemical biology, induction of biological processes via photoactivation is a powerful strategy for achieving spatiotemporal control. The importance of cysteine, glutathione, and other bioactive thiols in regulating protein structure/activity and cell redox homeostasis makes modulation of thiol activity particularly useful. One major objective for enhancing the utility of photoactivatable protecting groups (PPGs) in living systems is creating PPGs with longer wavelength absorption maxima and efficient two-photon (TP) absorption. Toward these objectives, we developed a carboxyl- and dimethylamine-functionalized nitrodibenzofuran PPG scaffold (cDMA-NDBF) for thiol photoactivation, which has a bathochromic shift in the one-photon absorption maximum from λmax = 315 nm with the unfunctionalized NDBF scaffold to λmax = 445 nm. While cDMA-NDBF-protected thiols are stable in the presence of UV irradiation, they undergo efficient broad-spectrum TP photolysis at wavelengths as long as 900 nm. To demonstrate the wavelength orthogonality of cDMA-NDBF and NDBF photolysis in a biological setting, caged farnesyltransferase enzyme inhibitors (FTI) were prepared and selectively photoactivated in live cells using 850-900 nm TP light for cDMA-NDBF-FTI and 300 nm UV light for NDBF-FTI. These experiments represent the first demonstration of thiol photoactivation at wavelengths above 800 nm. Consequently, cDMA-NDBF-caged thiols should have broad applicability in a wide range of experiments in chemical biology and materials science.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:19

Enthalten in:

Organic & biomolecular chemistry - 19(2021), 10 vom: 18. März, Seite 2213-2223

Sprache:

Englisch

Beteiligte Personen:

Hammers, Matthew D [VerfasserIn]
Hodny, Michael H [VerfasserIn]
Bader, Taysir K [VerfasserIn]
Mahmoodi, M Mohsen [VerfasserIn]
Fang, Sifei [VerfasserIn]
Fenton, Alexander D [VerfasserIn]
Nurie, Kadiro [VerfasserIn]
Trial, Hallie O [VerfasserIn]
Xu, Feng [VerfasserIn]
Healy, Andrew T [VerfasserIn]
Ball, Zachary T [VerfasserIn]
Blank, David A [VerfasserIn]
Distefano, Mark D [VerfasserIn]

Links:

Volltext

Themen:

Benzofurans
EC 2.5.1.29
Enzyme Inhibitors
Farnesyltranstransferase
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Sulfhydryl Compounds

Anmerkungen:

Date Completed 19.07.2021

Date Revised 15.09.2021

published: Print

Citation Status MEDLINE

doi:

10.1039/d0ob01986k

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM319144410