Design of Turn‐On Near‐Infrared Fluorescent Probes for Highly Sensitive and Selective Monitoring of Biopolymers

Ducharme, Gerard T.; LaCasse, Zane; Sheth, Tanya; Nesterova, Irina V.

doi:10.1002/anie.202000108

Cited by 14 publications

(12 citation statements)

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“…In the presence of nanomolar concentrations of EGFR kinase, the anchor’s selective binding to the target kinase causes partial deaggregation of the ZnPc fluorophore and generation of near-IR fluorescent emission in a concentration-dependent manner. At the same time, sensor 1 does not show nonselective binding and displays no fluorescent response to other biomacromolecules . Despite the promising performance of 1 in cell-free environments, the transition to cellular imaging encountered major obstacles.…”

Section: Resultsmentioning

confidence: 99%

“…First, we found that 1 was insufficiently water-soluble. Indeed, the in vitro target response experiments required an aqueous medium with 10% DMSO to produce a fluorescent signal . Such conditions are obviously not ideal (if even achievable) for live-cell imaging.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, we have developed the Pc sensor compound 1 (Scheme 1). 34 Under cell-free and in vitro conditions, this compound acts as a selective turn-on fluorescent sensor for EGFR tyrosine kinase. The molecular structure of 1 consists of two domains: a target-binding "anchor" and a linked phthalocyanine (Pc) fluorescent reporter.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…The synthesis of compound 1 has been described elsewhere. 34 EGFR Kinase/Sensor 2 Binding in Cell-Free Environments. EGFR kinase was reconstituted in a buffer consisting of 50 mM HEPES, 20 mM MgCl 2 , 100 μM MnCl 2 , and 200 μM Na 3 VO 4 at pH 7.4.…”

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confidence: 99%

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Zero-Background Small-Molecule Sensors for Near-IR Fluorescent Imaging of Biomacromolecular Targets in Cells

et al. 2023

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In this study, we report a general approach to the design of a new generation of small-molecule sensors that produce a zero background but are brightly fluorescent in the near-IR spectral range upon selective interaction with a biomolecular target. We developed a fluorescence turn-on/-off mechanism based on the aggregation/deaggregation of phthalocyanine chromophores. As a proof of concept, we designed, prepared, and characterized sensors for in-cell visualization of epidermal growth factor receptor (EGFR) tyrosine kinase. We established a structure/bioavailability correlation, determined conditions for the optimal sensor uptake and imaging, and demonstrated binding specificity and applications over a wide range of treatment options involving live and fixed cells. The new approach enables high-contrast imaging and requires no in-cell chemical assembly or postexposure manipulations (i.e., washes). The general design principles demonstrated in this work can be extended toward sensors and imaging agents for other biomolecular targets.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Zero-Background Small-Molecule Sensors for Near-IR Fluorescent Imaging of Biomacromolecular Targets in Cells

et al. 2023

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“…Using smart near-infrared (NIR) fluorescence imaging probes constructed from organic molecules to target specific cellular organelles is an emerging field of contemporary research . NIR fluorescent biomarkers (650–900 nm) for intracellular locations are indispensable in contrast with visible and other fluorescent dyes because NIR light can permeate deep tissues and offers a meaningful bioimaging method with negligible autofluorescence background . Mitochondria are crucial targets within the numerous cellular organelles .…”

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Design and Synthesis of Near-Infrared Mechanically Interlocked Molecules for Specific Targeting of Mitochondria

et al. 2020

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Bromide (CTAB), and Zinc phthalocyanine were obtained from TCI Chemicals. NMR solvents were purchased from Cambridge Isotope Laboratories, Inc. Epithelioid cervix carcinoma HeLa and lung adenocarcinoma A549 cell lines and normal human embryonic kidney (HEK293) cell line were acquired from The National Centre for Cell Science, India. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT), Dulbecco's modified eagle medium (DMEM), Trypsin EDTA mixture, Fetal Bovine Serum (FBS), and Antibiotic Antimycotic Solution were obtained from Himedia. MitoTracker Green was procured from Thermo Fisher Scientific. METHODS Microwave Synthesizer: Unsymmetrical MSQ and MSQRot were constructed using microwave synthesizer (CEM corporation, USA make, model discover bio). NMR Spectroscopy: 1D (1 H, 13 C, 31 P) and 2D NMR (1 H-1 H DQF COSY) were measured on Bruker DPX500 MHz, Bruker DPX400 MHz, and Bruker DPX300 MHz spectrometers at 25C in appropriate deuterated solvents. HRMS (ESI): High-resolution electrospray ionisation mass spectrometry (HRMS-ESI) was recorded using a Q-Tofmicro TM (Waters Corporation) mass spectrometer. Single Crystal X-Ray Diffraction: Single crystals suitable for X-ray diffraction was obtained by vapor diffusion method. A solution of SQRot in CHCl 3 was placed in a 2 mL vial and put inside a 20 mL vial filled with EtOAc. The larger vial was capped and allow to slow diffusion of EtOAc into CHCl 3 solution of the compound. Diffraction data of SQRot was measured with MoK α radiation (a graded multilayer mirror monochromator, λ = 0.71073 Å) at 273 K on a micro focus Single Crystal X-ray Diffraction instrument (Make: Bruker, Model : D8 Quest). A PHOTON-100 CMOS detector is used. Structures were solved by direct methods using the SHELXT 2014/5 program. S1,S2 Refinements were carried out with a full-matrix least squares method against F 2 using SHELXL-2018/3 S1,S2 incorporated in Olex2 S3 crystallographic collective package. The non-hydrogen atoms were refined with anisotropic thermal parameters. Formula sum = C97.24 H84 N6 O12, formula weight = 1528.58, crystal system = triclinic, space group = P-1, a = 11.1202(11) Å, b = 11.6727(12) Å, c = 16.8575(17) Å,  = 94.197(3),  = 100.651(3),  = 111.900(3), V = 1970.9(3) Å 3 , Z = 1, D calcd = 1.288 g cm 3 , μ = 0.085 mm 1. The final R value was R 1 = 0.0688 and wR 2 = 0.1875 for reflections with I > 2ζ(I).

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Modular Design and Scaffold‐Synthesis of Multi‐Functional Fluorophores for Targeted Cellular Imaging and Pyroptosis

Zhang,

Wang,

et al. 2024

Angewandte Chemie

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Fluorophores are essential tools for optical imaging and biomedical research. Their synthetic modification to incorporate new functions, however, remains a challenging task. Conventional strategies rely on linear synthesis in which a parent framework is gradually extended. We here designed and synthesized a versatile library of multi‐functional fluorophores via a scaffold‐based Ugi four‐component reaction (U‐4CR). The adaptability of the scaffold is achieved through modification of starting materials. This allows to use a small range of starting materials for the creation of fluorogenic probes that can detect reactive‐oxygen species and where the localization into subcellular organelles or membranes can be controlled. We present reaction yields ranging from 60 % to 90 % and discovered that some compounds can even function as imaging and therapeutic agents via Fenton chemistry inducing pyroptosis in living cancer cells. Our study underlines the potential of scaffold‐based synthesis for versatile creation of functional fluorophores and their applications.

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Design of Turn‐On Near‐Infrared Fluorescent Probes for Highly Sensitive and Selective Monitoring of Biopolymers

Cited by 14 publications

References 68 publications

Zero-Background Small-Molecule Sensors for Near-IR Fluorescent Imaging of Biomacromolecular Targets in Cells

Zero-Background Small-Molecule Sensors for Near-IR Fluorescent Imaging of Biomacromolecular Targets in Cells

Design and Synthesis of Near-Infrared Mechanically Interlocked Molecules for Specific Targeting of Mitochondria

Modular Design and Scaffold‐Synthesis of Multi‐Functional Fluorophores for Targeted Cellular Imaging and Pyroptosis

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