Rational design of small molecule fluorescent probes for biological applications

Jun, Joomyung V.; Chenoweth, David M.; Petersson, E. James

doi:10.1039/d0ob01131b

Cited by 168 publications

(116 citation statements)

References 107 publications

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“…We found that our fluorescent xanthene-based dyes TMR-d12 and SiR-d12 are improved by hydrogen-deuterium exchange on their methyl groups, enhancing photophysical parameters, such as brightness and lifetime, while reducing critical chemical parameters, such as bleaching. While the exact reason for this is unknown, we argue the following: i) affecting the rotation around the aromatic carbonnitrogen bond (in our case due to higher mass of the CD3 groups) has marked effects on fluorescent properties [17] , which could suppress non-radiative decays and in turn enhances quantum yield and lifetime [6] ; and ii) a lower zero-point energy of the C-D vs. C-H bond results in slower reaction kinetics, as an higher energy barrier has to be overcome [18] , and this could reduce bleaching through for example generated reactive oxygen species. While these explanations need more experimentation, ideally in combination with in silico calculations, we showcase novel deuterated dyes that outperform their parent molecules in multiple experiments, ranging from in vitro FRET, to live cellular labelling and sorting, in lifetime and super-resolution microscopy.…”

Section: Main Textmentioning

confidence: 87%

Deuterated rhodamines for protein labelling in nanoscopy

Roßmann

Akkaya

Charbonnier

et al. 2020

Preprint

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Rhodamine molecules are setting benchmarks in fluorescence microscopy. Herein, we report the deuterium (d12) congeners of tetramethyl(silicon)rhodamine, obtained by isotopic labelling of the four methyl groups, which improves photophysical (i.e. brightness, lifetimes) and chemical (i.e. bleaching) properties. We explore this finding for SNAP- and Halo-tag labelling, and highlight enhanced properties in several applications, such as Foerster resonance energy transfer, fluorescence activated cell sorting, fluorescence lifetime microscopy and stimulated emission depletion nanoscopy. We envision deuteration as a generalizable concept to improve existing and develop new Chemical Biology Probes.

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Section: Main Textmentioning

confidence: 87%

Deuterated rhodamines for protein labelling in nanoscopy

Roßmann

Akkaya

Charbonnier

et al. 2020

Preprint

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“…Tracking of individual viral proteins during viral disassembly, uncoating, or nuclear events should allow precise determination of the viral core remodeling mechanism. Likewise, additional information can be provided by using functional fluorescent probes capable of detecting environmental properties such as viscosity, polarity, membrane tension or pH [ 109 , 110 , 111 , 112 , 113 ]. Imaging of these probes conjugated to viral proteins will provide new original data on the physico-chemical characteristics of the intraviral environment and will highlight the modifications of the viral complexes linked to their remodeling during the early steps of infection.…”

Section: Discussionmentioning

confidence: 99%

Imaging Viral Infection by Fluorescence Microscopy: Focus on HIV-1 Early Stage

Mukherjee

Boutant²,

Réal³

et al. 2021

Viruses

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During the last two decades, progresses in bioimaging and the development of various strategies to fluorescently label the viral components opened a wide range of possibilities to visualize the early phase of Human Immunodeficiency Virus 1 (HIV-1) life cycle directly in infected cells. After fusion of the viral envelope with the cell membrane, the viral core is released into the cytoplasm and the viral RNA (vRNA) is retro-transcribed into DNA by the reverse transcriptase. During this process, the RNA-based viral complex transforms into a pre-integration complex (PIC), composed of the viral genomic DNA (vDNA) coated with viral and host cellular proteins. The protective capsid shell disassembles during a process called uncoating. The viral genome is transported into the cell nucleus and integrates into the host cell chromatin. Unlike biochemical approaches that provide global data about the whole population of viral particles, imaging techniques enable following individual viruses on a single particle level. In this context, quantitative microscopy has brought original data shedding light on the dynamics of the viral entry into the host cell, the cytoplasmic transport, the nuclear import, and the selection of the integration site. In parallel, multi-color imaging studies have elucidated the mechanism of action of host cell factors implicated in HIV-1 viral cycle progression. In this review, we describe the labeling strategies used for HIV-1 fluorescence imaging and report on the main advancements that imaging studies have brought in the understanding of the infection mechanisms from the viral entry into the host cell until the provirus integration step.

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“…So far, several FL imaging materials have been developed, and these materials can be mainly divided into two categories: organic molecules and inorganic nanomaterials. [140,141] Generally, most organic dyes suffer from photobleaching or phototoxicity. In recent years, some luminescent inorganic nanomaterials, such as quantum dots, rare‐earth doped NPs, and carbon materials, have also found potential applications in bioimaging.…”

Section: Bioimagingmentioning

confidence: 99%

Luminescent metal nanoclusters: Biosensing strategies and bioimaging applications

et al. 2021

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Metal nanoclusters (MNCs) are ultrasmall metal‐organic aggregates, composed of a metal core less than 2 nm and a protecting shell of metal‐organic ligand motifs. The controlled aggregation of metal atoms (in the cluster core) and metal‐organic ligand motifs (around the cluster core) renders MNCs with numerous molecule‐like properties, among which strong and bright luminescence has attracted extensive basic and applied interests. It has now known that aggregation‐induced emission is a feasible mechanism for controlling luminescence of MNCs, which makes it particularly useful in biosensing and bioimaging applications. Although the luminescence fundamentals and design principles largely determine the practicality and effectiveness of MNCs in biosensing and bioimaging applications, a systematic summary of this topic is lacking in the current literature. In this review, we aim to provide a concise discussion of the latest developments in biosensing and bioimaging applications of luminescent MNCs, highlighting their luminescence mechanisms, biosensing principles, and bioimaging strategies. Specifically, we first introduce the recent advances in the synthetic chemistry of MNCs, and then briefly discuss the luminescence fundamentals of MNCs. Then the design strategy and practicality of luminescent MNCs in biosensing and bioimaging applications are exemplified. We conclude the review with our perspectives on the further development of MNC‐based optical probes in biosensing and bioimaging applications. Our review is expected to provide guidance for the future practice of designing and synthesizing luminescent MNCs for biomedical and other applications.

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Rational design of small molecule fluorescent probes for biological applications

Abstract: Guidelines based on photophysical tuning, reactivity, isomerization, and energy transfer for rational design of synthetic fluorescent probes for biological systems.

Cited by 168 publications

References 107 publications

Deuterated rhodamines for protein labelling in nanoscopy

Deuterated rhodamines for protein labelling in nanoscopy

Imaging Viral Infection by Fluorescence Microscopy: Focus on HIV-1 Early Stage

Luminescent metal nanoclusters: Biosensing strategies and bioimaging applications

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