Rapid Access to a Broad Range of 6'-Substituted Firefly Luciferin Analogues Reveals Surprising Emitters and Inhibitors.
TL;DR: Two-step route to a broad range of 6'-substituted luciferin analogues was developed to enable more extensive study of the 6'-functionality and revealed thioether inhibitors and unexpectedly luminogenic aryl amine derivatives.
About: This article is published in Organic Letters.The article was published on 2017-10-17 and is currently open access. It has received 38 citations till now. The article focuses on the topics: Firefly luciferin & Luciferin.
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TL;DR: Recent advances in bioluminescent tool discovery and development are highlighted, along with applications of the probes in cells, tissues, and organisms, improving in vivo imaging capabilities and bolstering new research directions.
79 citations
TL;DR: This review highlights how bioluminescent systems are being leveraged not just for sensing-but also controlling-biological processes, and showcases how new luciferins and engineered luciferases are expanding the scope of optical imaging.
52 citations
TL;DR: Many fluorophores, and all bright light-emitting substrates for firefly luciferase, contain hydroxyl or amine electron donors, and sulfonamides were found to be capable of serving as replacements for these canonical groups.
26 citations
TL;DR: The goal was to generate multiple orthogonal luciferases that are responsive to unique scaffolds and could be used concurrently in living animals, and to develop Orthogonal bioluminescent probes that can selectively process luciferin analogs to produce light.
Abstract: ConspectusBioluminescence is widely used for real-time imaging in living organisms. This technology features a light-emitting reaction between enzymes (luciferases) and small molecule substrates (l...
25 citations
TL;DR: The results provide valuable insights for the design and optimization of novel fluorophores operating in the far-red/NIR region, since it is demonstrated that three important parameters cannot be always simultaneously addressed by simply replacing a N,N-dialkylamino group with azetidine, at least in nonconventional coumarin-based fluorideophores.
Abstract: Replacement of electron-donating N,N-dialkyl groups with three- or four-membered cyclic amines (e.g., aziridine and azetidine, respectively) has been described as a promising approach to improve some of the drawbacks of conventional fluorophores, including low fluorescent quantum yields (ΦF) in polar solvents. In this work, we have explored the influence of azetidinyl substitution on nonconventional coumarin-based COUPY dyes. Two azetidine-containing scaffolds were first synthesized in four linear synthetic steps and easily transformed into far-red/NIR-emitting fluorophores through N-alkylation of the pyridine moiety. Azetidine introduction in COUPY dyes resulted in enlarged Stokes’ shifts with respect to the N,N-dialkylamino-containing parent dyes, but the ΦF were not significantly modified in aqueous media, which is in contrast with previously reported observations in other fluorophores. However, azetidinyl substitution led to an unprecedented improvement in the photostability of COUPY dyes, and high ce...
24 citations
References
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TL;DR: Inspired by molecular modeling, the N,N-dimethylamino substituents in tetramethylrhodamine are replaced with four-membered azetidine rings, which doubles the quantum efficiency and improves the photon yield of the dye in applications ranging from in vitro single-molecule measurements to super-resolution imaging.
Abstract: Specific labeling of biomolecules with bright fluorophores is the keystone of fluorescence microscopy. Genetically encoded self-labeling tag proteins can be coupled to synthetic dyes inside living cells, resulting in brighter reporters than fluorescent proteins. Intracellular labeling using these techniques requires cell-permeable fluorescent ligands, however, limiting utility to a small number of classic fluorophores. Here we describe a simple structural modification that improves the brightness and photostability of dyes while preserving spectral properties and cell permeability. Inspired by molecular modeling, we replaced the N,N-dimethylamino substituents in tetramethylrhodamine with four-membered azetidine rings. This addition of two carbon atoms doubles the quantum efficiency and improves the photon yield of the dye in applications ranging from in vitro single-molecule measurements to super-resolution imaging. The novel substitution is generalizable, yielding a palette of chemical dyes with improved quantum efficiencies that spans the UV and visible range.
1,140 citations
TL;DR: In this paper, the effect of the bite angle on regioselectivity in the rhodium-catalyzed hydroformylation reaction was studied with a series of bidentate diphosphines based on xanthene-like backbones as ligands.
735 citations
TL;DR: A general method for the intermolecular coupling of aryl halides and amides using a Xantphos/Pd catalyst is described, and the desired C-N bond forming process proceeds in good to excellent yields with 1-4 mol % of the Pd catalyst.
Abstract: A general method for the intermolecular coupling of aryl halides and amides using a Xantphos/Pd catalyst is described. This system displays good functional group compatibility, and the desired C−N bond forming process proceeds in good to excellent yields with 1−4 mol % of the Pd catalyst. Additionally, the arylation of sulfonamides, oxazolidinones, and ureas is reported. The efficiency of these transformations was found to be highly dependent on reaction concentrations and catalyst loadings. A Pd complex resulting from oxidative addition of 4-bromobenzonitrile, (Xantphos)Pd(4-cyanophenyl)(Br) (II), was prepared in one step from Xantphos, Pd2(dba)3, and the aryl bromide. Complex II proved to be an active catalyst for the coupling between 4-bromobenzonitrile and benzamide. X-ray crystallographic analysis of II revealed a rare trans-chelating bisphosphine-Pd(II) structure with a large bite angle of 150.7°.
438 citations
TL;DR: A general strategy for dual-analyte detection in living animals that employs in situ formation of firefly luciferin from two complementary caged precursors that can be unmasked by different biochemical processes is presented.
Abstract: In vivo molecular imaging holds promise for understanding the underlying mechanisms of health, injury, aging, and disease, as it can detect distinct biochemical processes such as enzymatic activity, reactive small-molecule fluxes, or post-translational modifications. Current imaging techniques often detect only a single biochemical process, but, within whole organisms, multiple types of biochemical events contribute to physiological and pathological phenotypes. In this report, we present a general strategy for dual-analyte detection in living animals that employs in situ formation of firefly luciferin from two complementary caged precursors that can be unmasked by different biochemical processes. To establish this approach, we have developed Peroxy Caged Luciferin-2 (PCL-2), a H2O2-responsive boronic acid probe that releases 6-hydroxy-2-cyanobenzothiazole (HCBT) upon reacting with this reactive oxygen species, as well as a peptide-based probe, z-Ile-Glu-ThrAsp-d-Cys (IETDC), which releases d-cysteine in t...
259 citations
TL;DR: A novel protein labeling method that uses a single amino-acid tag — N-terminal cysteine residue — and small-molecule probes carrying the cyanobenzothiazole unit for specific labeling of proteins in vitro and at the surface of live cells is described.
Abstract: This communication describes a novel protein labeling method that uses a single amino-acid tag — N-terminal cysteine residue — and small-molecule probes carrying the cyanobenzothiazole unit for specific labeling of proteins in vitro and at the surface of live cells. This simple ligation reaction proceeds with a high degree of specificity in physiological conditions, and should offer an important alternative to currently available protein labeling methods.
205 citations