Strategies in the Design of Small‐Molecule Fluorescent Probes for Peptidases

Chen, Laizhong; Li, Jing; Du, Lüpei; Li, Minyong

doi:10.1002/med.21316

Cited by 27 publications

(12 citation statements)

References 99 publications

(169 reference statements)

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“…In general, the typical fluorescent probe consists of three parts: a fluorophore, a pharmacophore, and a linker (Cohen et al, 2002; Chen et al, 2014; Mizukami et al, 2014). In consideration of good fluorescent properties of TPE, it has been chosen as the fluorophore in the rational design for hERG channels probe.…”

Section: Resultsmentioning

confidence: 99%

Aggregation-Induced Emission: Lighting Up hERG Potassium Channel

Zhang

Liu

et al. 2019

Front. Chem.

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Based on the scaffold of astemizole and E-4031, four AIE light-up probes (L1–L4) for Human Ether-a-go-go-Related Gene (hERG) potassium channel were developed herein using AIE fluorogen(TPE). These probes showing advantages such as low background interference, superior photostability, acceptable cell toxicity, and potent inhibitory activity, which could be used to image hERG channels at the nanomolar level. These AIE light-up probes hoped to provide guidelines for the design of more advanced AIE sensing and imaging hERG channels to a broad range of applications.

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Section: Resultsmentioning

confidence: 99%

Aggregation-Induced Emission: Lighting Up hERG Potassium Channel

Zhang

Liu

et al. 2019

Front. Chem.

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“…35 6. RECOGNITION MOIETIES OF FLUORESCENT PROBES FOR SEVERAL AMNIOPEPTIDASES Aminopeptidases specifically hydrolyze peptide bonds of some proteins, 36,37 and therefore, their recognition moieties are usually constructed with the corresponding amino acids, which can be engineered onto fluorophores via an amide bond. 17 In this way, we have developed different fluorescent probes for several aminopeptidases, including γ-glutamyl transpeptidase (GGT), leucine aminopeptidase (LAP), aminopeptidase N (APN), pyroglutamate aminopeptidase 1 (PGP-1), pantetheinase, dipeptide peptidase IV (DPPIV), and fibroblast activation protein (FAP).…”

Section: -Nitrobenzyl Alcoholmentioning

confidence: 99%

Recognition Moieties of Small Molecular Fluorescent Probes for Bioimaging of Enzymes

et al. 2019

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Conspectus Enzymes are a class of important substances for life, and their abnormal levels are associated with many diseases. Thus, great progress has been made in the past decade in detecting and imaging enzymes in living biosystems, and in this respect fluorescent probes combined with confocal microscopy have attracted much attention because of their high sensitivity and unrivaled spatiotemporal resolution. Fluorescent probes are usually composed of three moieties: a signal or fluorophore moiety, a recognition or labeling moiety, and an appropriate linker to connect the two aforementioned moieties. At present, however, research and reviews on enzymatic probes mostly focus on fluorophores and/or linkers, whereas those on the recognition moiety are relatively few. Moreover, current enzymatic probes with some recognition moieties have drawbacks such as poor selectivity, high background fluorescence, or/and low sensitivity and are unsatisfactory for practical applications. Thus, developing new recognition moieties with higher specificity or/and sensitivity to the enzyme of interest is very desirable but still challenging. In this Account, we introduce the recognition moieties of fluorescent probes for several enzymes, including tyrosinase, monoamine oxidase A (MAO-A), nitroreductase (NTR), and aminopeptidases. Highlights are given on how new specific recognition moieties of tyrosinase and MAO-A were designed to eliminate the interference by reactive oxygen species (ROS) and MAO-B, respectively. Here we present four recent examples in which designed fluorescent probes are employed to image enzymes in living biosystems. The first example shows that 3-hydroxyphenyl can serve as a new and more specific recognition moiety than the traditional 4-hydroxyphenyl group for tyrosinase, enabling the development of a highly selective fluorescent probe for imaging of tyrosinase without interference by ROS. The second presents a general design strategy for fluorescent probes specific for an enzyme, which involves combining the characteristic structure of an inhibitor of the target enzyme along with its traditional reactive group as a new recognition moiety, and successfully demonstrates it by selective detection of MAO-A in the presence of its isomeric MAO-B. The third mainly illustrates that 5-nitrothiophen-2-yl alcohol with a stronger electron-donating S atom is a better fluorescence quenching and recognition moiety than 5-nitrofuran-2-yl alcohol for NTR, leading to the development of a highly sensitive method for NTR assay. Lastly, on the basis of known observations, we show that besides the specific interaction with the target, another function of some recognition moieties may be responsible for tuning the fluorescence signal, which is exemplified by the linking of several aminopeptidases’ recognition moieties to the free hydroxyl or amino group of different fluorophores. It is our wish that this Account will promote the appearance of more specific recognition moieties and fluorescent probes with excellent properties and that...

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“…Commercialized fluorescein/rhodamine-based dyes (e.g., MitoTracker [24]) are being used daily in a vast amount of chemical, biological or medical research laboratories. These molecules are utilized to visualize and quantify a multitude of static or dynamic processes in living cells due to their high sensitivity, real-time detection, and non-destructive fast analysis [25][26][27]. The probes can target a variety of biological targets due to their structural adjustability [28][29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

Recent Progress in Small Spirocyclic, Xanthene-Based Fluorescent Probes

2020

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The use of fluorescent probes in a multitude of applications is still an expanding field. This review covers the recent progress made in small molecular, spirocyclic xanthene-based probes containing different heteroatoms (e.g., oxygen, silicon, carbon) in position 10′. After a short introduction, we will focus on applications like the interaction of probes with enzymes and targeted labeling of organelles and proteins, detection of small molecules, as well as their use in therapeutics or diagnostics and super-resolution microscopy. Furthermore, the last part will summarize recent advances in the synthesis and understanding of their structure–behavior relationship including novel computational approaches.

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Strategies in the Design of Small‐Molecule Fluorescent Probes for Peptidases

Cited by 27 publications

References 99 publications

Aggregation-Induced Emission: Lighting Up hERG Potassium Channel

Aggregation-Induced Emission: Lighting Up hERG Potassium Channel

Recognition Moieties of Small Molecular Fluorescent Probes for Bioimaging of Enzymes

Recent Progress in Small Spirocyclic, Xanthene-Based Fluorescent Probes

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