Electrophilic, Activation-Free Fluorogenic Reagent for Labeling Bioactive Amines

Abstract

Herein we report the preparation of BODIPY mesoionic acid fluorides through a short sequence involving an isocyanide multicomponent reaction as the key synthetic step. These novel BODIPY acid fluorides are water-stable electrophilic reagents that can be used for the fluorescent derivatization of amine-containing biomolecules using mild and activation-free reaction conditions. As a proof of principle, we have labeled the antifungal natamycin and generated a novel fluorogenic probe for imaging a variety of human and plant fungal pathogens, with excellent selectivity over bacterial cells.

Fluorescent cyclic peptides for cell imaging

“…[ 33 ] Some PeT‐dependent BODIPY fluorophore systems have been found to be sensitive to the polarity environment, showing increased fluorescence quenching in different microenvironments or upon binding to various analytes. [ 34–39 ]…”

“…[33] Some PeT-dependent BODIPY fluorophore systems have been found to be sensitive to the polarity environment, showing increased fluorescence quenching in different microenvironments or upon binding to various analytes. [34][35][36][37][38][39] Depending on the anchoring functional groups, the incorporation of the fluorescent moiety into the cyclic peptide is performed either before or after the cyclisation step through different covalent linkages such as amide, [40][41][42] thioamide, [43] and thioether [44] bonds, the former being the most widely applied ( Figure 1D). [45] Additionally, numerous attempts have been made to explore alternative approaches.…”

Moderne Strategien zur Synthese funktioneller Fluorophore

“…Vor kurzem wurde dieser Ansatz auf Isochinolin‐substituierte BODIPY‐Strukturen ausgeweitet. Die daraus resultierenden mesoionischen BODIPY‐Verbindungen wurden zur aktivierungslosen Markierung von bioaktiven Aminen verwendet, und ein fluoreszierendes Analogon des antimykotischen Agens Natamycin wurde für die Abbildung von Pilzzellen entwickelt (Abbildung C) …”

“…TFAA=Trifluoressigsäureanhydrid. Wiedergabe mit Genehmigung der Royal Society of Chemistry (A) und der American Chemical Society (C) …”

Fluorescent peptides for imaging of fungal cells

“…In the last decades, multiple chemical approaches have been reported for the development of fluorescent probes that enable direct visualisation of biomolecules and cells. These encompass broad diversityoriented fluorescent libraries to identify novel biomarkers of cell states [4] as well as reactive fluorophores for targeted conjugation to small molecules and drugs [5][6][7]. Major advantages of fluorescent probes include: 1) high sensitivity with typically low limits of detection [8][9][10], 2) compatibility for multiplexed assays [11,12], and 3) high versatility in multiple assay formats, from mechanistic studies [13,14] to high-throughput screenings [15] and in vivo imaging [16].…”