Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 230
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Chem Sci ; 12(40): 13483-13491, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34777768

RESUMO

Diagnosing aging for preventative intervention generally relies on the tracking of aging biomarkers in the resting state. However, the static marker levels are insufficient to fully evaluate aging, particularly given that the stress response capacity (SRC) decay is currently viewed as a critical feature of aging. Therefore, we have developed a dual-channel fluorescent probe ROKS capable of the logic-based visualization of thiophenol (stressor) and HOCl (thiophenol-activated stress response product) in vivo, which provides a new strategy from the time dimension to precisely assess the SRC of individuals under stress using the dual-channel fluorescence ratio. Using ROKS we observed that the SRC of live cells decayed with senescence, and that a higher SRC was found for young vs. aged Caenorhabditis elegans. As such, our study offers a promising strategy for the fluorescence-guided diagnosis of aging and paves the way for accurate evaluation of the efficacy of anti-aging drugs.

2.
Front Chem ; 9: 767847, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778216

RESUMO

Bacterial infection is a major threat to human health. However, many antibacterial agents currently used are severely limited due to drug-resistance, and the development of side effects. Herein, we have developed a non-antibiotic nanocomposite consisting of chitosan (ChS) coated silver nanoparticles (AgNPs) and graphene nanoribbon (GNR)-based nanowires for light-triggered eradication of bacteria. The presence of AgNP/ChS significantly enhanced the interactions of the GNR nanowires with Pseudomonas aeruginosa, a clinically common Gram-negative bacterium. Which enables the highly effective photothermal eradication of bacteria by GNR upon near-infrared light irradiation. The nanocomposite was shown to be applicable for the light-triggered eradication of bacterial biofilms and the inhibition of bacterial growth on medical patches used for abdominal-wall hernia surgery.

3.
Chem Commun (Camb) ; 57(84): 11084-11087, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34617087

RESUMO

Excited-state intramolecular proton transfer (ESIPT)-based fluorophores with two-photon excitation fluorescence (TPEF) are rare. Our aim with this research was to develop ESIPT-based fluorophores exhibiting TPEF. Herein, we used 4-hydroxyisoindoline-1,3-dione as a scaffold to develop a two-photon fluorescent probe BHID-Bpin, for the detection of peroxynitrite (ONOO-). BHID-Bpin exhibits excellent selectivity, sensitivity, and fast response towards ONOO- in PBS buffer solution (10 mM, pH = 7.40). Additionally, BHID-Bpin displays high photo-stability under two-photon irradiation at 750 nm. Furthermore, the probe can image endogenous ONOO- in HeLa cells and exogenous ONOO- in rat hippocampal slices at a depth of 110 µm.

4.
Chem Commun (Camb) ; 57(91): 12098-12110, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34714306

RESUMO

Biomacromolecular drugs have become an important class of therapeutic agents for the treatment of human diseases. Considering their high propensity for being degraded in the human body, the choice of an appropriate delivery system is key to ensure the therapeutic efficacy of biomacromolecular drugs in vivo. As an emerging class of supramolecular "host" materials, metal-organic frameworks (MOFs) exhibit advantages in terms of the tunability of pore size, encapsulation efficiency, controllable drug release, simplicity in surface functionalization and good biocompatibility. As a result, MOF-based host-guest systems have been extensively developed as a new class of flexible and powerful platform for the delivery of therapeutic biomacromolecules. In this review, we summarize current research progress in the synthesis of MOFs as delivery materials for a variety of biomacromolecules. Firstly, we briefly introduce the advances made in the use of biomacromolecular drugs for disease therapy and the types of commonly used clinical delivery systems. We then describe the advantages of using MOFs as delivery materials. Secondly, the strategies for the construction of MOF-encapsulated biomacromolecules (Biomacromolecules@MOFs) and the release mechanisms of the therapeutics are categorized. Thirdly, the application of MOFs to deliver different types of biomacromolecules (e.g., antigens/antibodies, enzymes, therapeutic proteins, DNA/RNA, polypeptides, and polysaccharides) for the treatment of various human diseases based on immunotherapy, gene therapy, starvation therapy and oxidation therapy is summarized. Finally, the remaining challenges and available opportunities for MOFs as drug delivery systems are outlined, which we anticipate will encourage additional research efforts directed towards developing Biomacromolecules@MOFs systems for biomedical applications.

5.
Anal Chem ; 93(43): 14471-14480, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34693710

RESUMO

α-Naphthyl acetate esterase (α-NAE) and acid α-naphthyl acetate esterase (ANAE), a class of special esterases, are important for lymphocyte typing and immunocompetence-monitoring. As such, the simultaneous detection of α-NAE and ANAE has become a target to effectively improve the accuracy in lymphocyte typing. Therefore, we developed a dual-factor synergistically activated ESIPT-based probe (HBT-NA) to detect α-NAE and ANAE sensitively, rapidly, and simultaneously in a differential manner. HBT-NA exhibits differential fluorescence signal outputs toward small changes of α-NAE and ANAE activities. HBT-NA displays a weak fluorescence signal at 392 nm over a pH range from 6.0 to 7.4. However, when it interacts with α-NAE (0-25 U) at pH = 7.4, the fluorescence intensity at 392 nm enhanced linearly within 60 s (F392 nm/F0392 nm = 0.042 Cα-NAE + 1.1, R2 = 0.99). Furthermore, HBT-NA emits ratiometric fluorescence signals (F505 nm/F392 nm) for ANAE (0-25 U) at pH = 6.0 within 2.0 min, exhibiting a good linear relationship (F505 nm/F392 nm = 0.83CANAE - 1.75, R2 = 0.99). The differential fluorescence signals can be used to simultaneously detect the activities of α-NAE and ANAE in solutions and complex living organisms. More importantly, based on the differential fluorescence signals toward α-NAE and ANAE, T lymphocytes and B lymphocytes could be successfully typed and differentiated among nontyped lymphocytes, facilitating the real-time evaluation of their immune functions using flow cytometry. Hence, HBT-NA could be used for the ultrasensitive detection of the enzyme activities of α-NAE and ANAE, the real-time precise typing of lymphocytes, and the monitoring of immunocompetence.


Assuntos
Naftol AS D Esterase , Linfócitos T , Linfócitos B , Naftóis
6.
Chem Commun (Camb) ; 57(81): 10608-10611, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34570136

RESUMO

AzuFluor® 435-DPA-Zn, an azulene fluorophore bearing two zinc(II)-dipicolylamine receptor motifs, exhibits fluorescence enhancement in the presence of adenosine diphosphate. Selectivity for ADP over ATP, AMP and PPi results from appropriate positioning of the receptor motifs, since an isomeric sensor cannot discriminate between ADP and ATP.

7.
Chem Sci ; 12(33): 11089-11097, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34522306

RESUMO

Triple negative breast cancer (TNBC) is one of the most malignant subtypes of breast cancer. Here, we report the construction of graphene nanoribbon (GNR)-based supramolecular ensembles with dual-receptor (mannose and αvß3 integrin receptors) targeting function, denoted as GNR-Man/PRGD, for targeted photothermal treatment (PTT) of TNBC. The GNR-Man/PRGD ensembles were constructed through the solution-based self-assembly of mannose-grafted GNRs (GNR-Man) with a pyrene-tagged αvß3 integrin ligand (PRGD). Enhanced PTT efficacies were achieved both in vitro and in vivo compared to that of the non-targeting equivalents. Tumor-bearing live mice were administered (tail vein) with GNR-Man/PRGD and then each mice group was subjected to PTT. Remarkably, GNR-Man/PRGD induced complete ablation of the solid tumors, and no tumor regrowth was observed over a period of 15 days. This study demonstrates a new and promising platform for the development of photothermal nanomaterials for targeted tumor therapy.

8.
ACS Sens ; 6(9): 3348-3356, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34469146

RESUMO

Nitroreductases (NTRs) mediate the reduction of nitroaromatic compounds to the corresponding nitrite, hydroxylamine, or amino derivatives. The activity of NTRs in bacteria facilitates the metabolic activation and antibacterial activity of 5-nitroimidazoles. Therefore, NTR activity correlates with the drug susceptibility and resistance of pathogenic bacteria. As such, it is important to develop a rapid and visual assay for the real-time sensing of bacterial NTRs for the evaluation and development of antibiotics. Herein, an activatable near-infrared fluorescent probe (HC-NO2) derived from a hemicyanine fluorophore was designed and developed based on two evaluation factors, including the calculated partition coefficient (Clog P) and fluorescence wavelength. Using HC-NO2 as the special substrate of NTRs, NTR activity can be assayed efficiently, and then, bacteria can be imaged based on the detection of NTRs. More importantly, a sensitive in-gel assay using HC-NO2 has been developed to selectively identify NTRs and sensitively determine NTR activity. Using the in-gel assay, NTRs from various bacterial species have been profiled visually from the "fluorescence fingerprints", which facilitates the rapid identification of NTRs from bacterial lysates. Thus, various homologous NTRs were identified from three metronidazole-susceptible bacterial species as well as seven unsusceptible species, which were confirmed by the whole-genome sequence. As such, the evaluation of NTRs from different bacterial species should help improve the rational usage of 5-nitroimidazole drugs as antibiotics.


Assuntos
Corantes Fluorescentes , Nitrorredutases , Bactérias , Nitrorredutases/genética
9.
Anal Chem ; 93(37): 12617-12627, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34494815

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease, and ß-amyloid (Aß) is believed to be a causative factor in AD pathology. The abnormal deposition of Aß is believed to be responsible for progression of AD. In order to facilitate the imaging of Aß in vivo, suitable probe molecules with a near-infrared emission wavelength that can penetrate the blood-brain barrier (BBB) were utilized. The commercial fluorescent probe thioflavin-T (ThT) is used to image Aß; however, because of its short emission wavelength and poor BBB penetration, ThT can only be used in vitro. With this research, based on ThT, we design three fluorescent probes (SZIs) having a longer emission wavelength in order to image Aß aggregates. SZIs with different numbers of double bonds respond to Aß aggregates. The SZIs have a structure similar to ThT, and as such, the SZIs are also unable to penetrate the BBB. To deal with the problem, we develop nanocomposites (MSN-Lf@SZIs) to deliver SZIs into the brain of AD mouse and image Aß successfully. These new nanocomposites are able to deliver the dyes into the brain and facilitate Aß imaging in vivo.


Assuntos
Nanocompostos , Doenças Neurodegenerativas , Peptídeos beta-Amiloides , Animais , Camundongos , Imagem Óptica , Dióxido de Silício
10.
Chem Soc Rev ; 50(21): 12098-12150, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34550134

RESUMO

The microenvironment (local environment), including viscosity, temperature, polarity, hypoxia, and acidic-basic status (pH), plays indispensable roles in cellular processes. Significantly, organelles require an appropriate microenvironment to perform their specific physiological functions, and disruption of the microenvironmental homeostasis could lead to malfunctions of organelles, resulting in disorder and disease development. Consequently, monitoring the microenvironment within specific organelles is vital to understand organelle-related physiopathology. Over the past few years, many fluorescent probes have been developed to help reveal variations in the microenvironment within specific cellular regions. Given that a comprehensive understanding of the microenvironment in a particular cellular region is of great significance for further exploration of life events, a thorough summary of this topic is urgently required. However, there has not been a comprehensive and critical review published recently on small-molecule fluorescent chemosensors for the cellular microenvironment. With this review, we summarize the recent progress since 2015 towards small-molecule based fluorescent probes for imaging the microenvironment within specific cellular regions, including the mitochondria, lysosomes, lipid drops, endoplasmic reticulum, golgi, nucleus, cytoplasmic matrix and cell membrane. Further classifications at the suborganelle level, according to detection of microenvironmental factors by probes, including polarity, viscosity, temperature, pH and hypoxia, are presented. Notably, in each category, design principles, chemical synthesis, recognition mechanism, fluorescent signals, and bio-imaging applications are summarized and compared. In addition, the limitations of the current microenvironment-sensitive probes are analyzed and the prospects for future developments are outlined. In a nutshell, this review comprehensively summarizes and highlights recent progress towards small molecule based fluorescent probes for sensing and imaging the microenvironment within specific cellular regions since 2015. We anticipate that this summary will facilitate a deeper understanding of the topic and encourage research directed towards the development of probes for the detection of cellular microenvironments.

11.
Angew Chem Int Ed Engl ; 60(46): 24566-24572, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34431597

RESUMO

UDP-glucuronosyltransferase 1A1 (UGT1A1) is a vital metabolic enzyme responsible for the clearance of endogenous substances and drugs. Hitherto, the development of fluorescent probes for UGTs was severely restricted due to the poor isoform selectivity and on-off or blue-shifted fluorescence response. Herein, we established a novel "molecular-splicing" strategy to construct a highly selective near-infrared (NIR) fluorescent probe, HHC, for UGT1A1, which exhibited a NIR signal at 720 nm after UGT1A1 metabolism. HHC was then successfully used for the real-time imaging of endogenous UGT1A1 in living cells and animals and to monitor the bile excretion function. In summary, an isoform-specific NIR fluorescent probe has been developed for monitoring UGT1A1 activity in living systems, high-throughput screening of novel UGT1A1 inhibitors and visual evaluation of bile excretion function.

12.
Chem Soc Rev ; 50(17): 9391-9429, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34232230

RESUMO

Chemical tools that allow the real-time monitoring of organ function and the visualisation of organ-related processes at the cellular level are of great importance in biological research. The upregulation/downregulation of specific biomarkers is often associated with the development of organ related diseases. Small-molecule fluorescent probes have the potential to create advances in our understanding of these disorders. Viable probes should be endowed with a number of key features that include high biomarker sensitivity, low limit of detection, fast response times and appropriate in vitro and in vivo biocompatibility. In this tutorial review, we discuss the development of probes that allow the targeting of organ related processes in vitro and in vivo. We highlight the design strategy that underlies the preparation of various promising probes, their optical response to key biomarkers, and proof-of-concept biological studies. The inherent drawbacks and limitations are discussed as are the current challenges and opportunities in the field. The hope is that this tutorial review will inspire the further development of small-molecule fluorescent probes that could aid the study of pathogenic conditions that contribute to organ-related diseases.

13.
Chem Sci ; 12(10): 3406-3426, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-34163615

RESUMO

Small-molecule based fluorescent probes are increasingly important for the detection and imaging of biological signaling molecules due to their simplicity, high selectivity and sensitivity, whilst being non-invasive, and suitable for real-time analysis of living systems. With this perspective we highlight sensing mechanisms including Förster resonance energy transfer (FRET), intramolecular charge transfer (ICT), photoinduced electron transfer (PeT), excited state intramolecular proton transfer (ESIPT), aggregation induced emission (AIE) and multiple modality fluorescence approaches including dual/triple sensing mechanisms (DSM or TSM). Throughout the perspective we highlight the remaining challenges and suggest potential directions for development towards improved small-molecule fluorescent probes suitable for biosensing.

14.
Chem Sci ; 12(11): 3921-3928, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34163661

RESUMO

Drug-induced liver injury (DILI) is an important cause of potentially fatal liver disease. Herein, we report the development of a molecular probe (LW-OTf) for the detection and imaging of two biomarkers involved in DILI. Initially, primary reactive oxygen species (ROS) superoxide (O2˙-) selectively activates a near-infrared fluorescence (NIRF) output by generating fluorophore LW-OH. The C[double bond, length as m-dash]C linker of this hemicyanine fluorophore is subsequently oxidized by reactive nitrogen species (RNS) peroxynitrite (ONOO-), resulting in cleavage to release xanthene derivative LW-XTD, detected using two-photon excitation fluorescence (TPEF). An alternative fluorescence pathway can occur through cleavage of LW-OTf by ONOO- to non-fluorescent LW-XTD-OTf, which can react further with the second analyte O2˙- to produce the same LW-XTD fluorescent species. By combining NIRF and TPEF, LW-OTf is capable of differential and simultaneous detection of ROS and RNS in DILI using two optically orthogonal channels. Probe LW-OTf could be used to detect O2˙- or O2˙- and ONOO- in lysosomes stimulated by 2-methoxyestradiol (2-ME) or 2-ME and SIN-1 respectively. In addition, we were able to monitor the chemoprotective effects of tert-butylhydroxyanisole (BHA) against acetaminophen (APAP) toxicity in living HL-7702 cells. More importantly, TPEF and NIRF imaging confirmed an increase in levels of both O2˙- and ONOO- in mouse livers during APAP-induced DILI (confirmed by hematoxylin and eosin (H&E) staining).

15.
Biomater Sci ; 9(12): 4433-4439, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34075906

RESUMO

Alkaline phosphatase (ALP) is an important enzyme-based biomarker present in several bacterial species; however, it is currently undervalued as a strategy to detect pathogenic bacteria. Here, we explore our ALP-responsive colorimetric and fluorescent probe (TCF-ALP) for such applications. TCF-ALP displayed a colorimetric and fluorescence response towards Staphylococcus aureus (S. aureus), with a limit of detection of 3.7 × 106 CFU mL-1 after 24 h incubation. To our surprise, TCF-ALP proved selective towards Staphylococcus bacteria when compared with Enterococcus faecalis (E. faecalis), and Gram-negative P. aeruginosa and E. coli. Selectivity was also seen in clinically relevant S. aureus biofilms. Owing to the high prevalence and surface location of S. aureus in chronic wounds, TCF-ALP was subsequently encapsulated in polyvinyl alcohol (PVA)-based hydrogels as a proof-of-concept "smart" wound dressing. TCF-ALP hydrogels were capable of detecting S. aureus in planktonic and biofilm assays, and displayed a clear colour change from yellow to purple after 24 h incubation using ex vivo porcine skin models. Overall, TCF-ALP is a simple tool that requires no prior knowledge, training, or specialist equipment, and has the potential to overcome issues related to invasive swabbing and tissue biopsy methods. Thus, TCF-ALP could be used as a tool to monitor the early development of infection in a wound and allow for the rapid provision of appropriate treatment for Staphylococcal bacterial infections.


Assuntos
Fosfatase Alcalina , Staphylococcus aureus , Animais , Bactérias , Bandagens , Biofilmes , Escherichia coli , Corantes Fluorescentes , Pseudomonas aeruginosa , Suínos
16.
Chem Soc Rev ; 50(10): 5952-5984, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34027955

RESUMO

Racemases and epimerases catalyse changes in the stereochemical configurations of chiral centres and are of interest as model enzymes and as biotechnological tools. They also occupy pivotal positions within metabolic pathways and, hence, many of them are important drug targets. This review summarises the catalytic mechanisms of PLP-dependent, enolase family and cofactor-independent racemases and epimerases operating by a deprotonation/reprotonation (1,1-proton transfer) mechanism and methods for measuring their catalytic activity. Strategies for inhibiting these enzymes are reviewed, as are specific examples of inhibitors. Rational design of inhibitors based on substrates has been extensively explored but there is considerable scope for development of transition-state mimics and covalent inhibitors and for the identification of inhibitors by high-throughput, fragment and virtual screening approaches. The increasing availability of enzyme structures obtained using X-ray crystallography will facilitate development of inhibitors by rational design and fragment screening, whilst protein models will facilitate development of transition-state mimics.


Assuntos
Inibidores Enzimáticos/metabolismo , Racemases e Epimerases/metabolismo , Regulação Alostérica , Biocatálise , Domínio Catalítico , Coenzimas/metabolismo , Desenho de Fármacos , Inibidores Enzimáticos/química , Simulação de Dinâmica Molecular , Prótons , Racemases e Epimerases/antagonistas & inibidores , Especificidade por Substrato
17.
J Mater Chem B ; 9(17): 3640-3661, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33870985

RESUMO

The excessive use of antibiotics has led to a rise in drug-resistant bacteria. These "superbugs" are continuously emerging and becoming increasingly harder to treat. As a result, new and effective treatment protocols that have minimal risks of generating drug-resistant bacteria are urgently required. Advanced nanomaterials are particularly promising due to their drug loading/releasing capabilities combined with their potential photodynamic/photothermal therapeutic properties. In this review, 0-dimensional, 1-dimensional, 2-dimensional, and 3-dimensional nanomaterial-based systems are comprehensively discussed for bacterial-based diagnostic and treatment applications. Since the use of these platforms as antibacterials is relatively new, this review will provide appropriate insight into their construction and applications. As such, we hope this review will inspire researchers to explore antibacterial-based nanomaterials with the aim of developing systems for clinical applications.


Assuntos
Antibacterianos/química , Portadores de Fármacos/química , Nanoestruturas/química , Fármacos Fotossensibilizantes/química , Animais , Antibacterianos/farmacologia , Carbono/química , Corantes/química , Terapia Combinada , Liberação Controlada de Fármacos , Resistência Microbiana a Medicamentos , Humanos , Metais/química , Conformação Molecular , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Polímeros/química , Propriedades de Superfície
18.
Org Biomol Chem ; 19(11): 2502-2511, 2021 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-33661271

RESUMO

Guaiazulene is an alkyl-substituted azulene available from natural sources and is a much lower cost starting material for the synthesis of azulene derivatives than azulene itself. Here we report an approach for the selective functionalisation of guaiazulene which takes advantage of the acidity of the protons on the guaiazulene C4 methyl group. The aldehyde produced by this approach constitutes a building block for the construction of azulenes substituted on the seven-membered ring. Derivatives of this aldehyde synthesised by alkenylation, reduction and condensation are reported, and the halochromic properties of a subset of these derivatives have been studied.

19.
Med Res Rev ; 41(4): 2039-2108, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33559917

RESUMO

Zika virus (ZIKV) has emerged as a particularly notorious mosquito-borne flavivirus, which can lead to a devastating congenital syndrome in the fetuses of pregnant mothers (e.g., microcephaly, spasticity, craniofacial disproportion, miscarriage, and ocular abnormalities) and cause the autoimmune disorder Guillain-Barre' syndrome of adults. Due to its severity and rapid dispersal over several continents, ZIKV has been acknowledged to be a global health concern by the World Health Organization. Unfortunately, the ZIKV has recently resurged in India with the potential for devastating effects. Researchers from all around the world have worked tirelessly to develop effective detection strategies and vaccines for the prevention and control of ZIKV infection. In this review, we comprehensively summarize the most recent research into ZIKV, including the structural biology and evolution, historical overview, pathogenesis, symptoms, and transmission. We then focus on the detection strategies for ZIKV, including viral isolation, serological assays, molecular assays, sensing methods, reverse transcription loop mediated isothermal amplification, transcription-mediated amplification technology, reverse transcription strand invasion based amplification, bioplasmonic paper-based device, and reverse transcription isothermal recombinase polymerase amplification. To conclude, we examine the limitations of currently available strategies for the detection of ZIKV, and outline future opportunities and research challenges.


Assuntos
Infecção por Zika virus , Zika virus , Adulto , Animais , Feminino , Humanos , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Gravidez , Zika virus/genética , Infecção por Zika virus/diagnóstico
20.
Angew Chem Int Ed Engl ; 60(19): 10756-10765, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33624914

RESUMO

The tracking of cellular senescence usually depends on the detection of senescence-associated ß-galactosidase (SA-ß-gal). Previous probes for SA-ß-gal with this purpose only cover a single dimension: the accumulation of this enzyme in lysosomes. However, this is insufficient to determine the destiny of senescence because endogenous ß-gal enriched in lysosomes is not only related to senescence, but also to some other physiological processes. To address this issue, we introduce our fluorescent probes including a second dimension: lysosomal pH, since de-acidification is a unique feature of the lysosomes in senescent cells. With this novel design, our probes achieved excellent discrimination of SA-ß-gal from cancer-associated ß-gal, which enables them to track cellular senescence as well as tissue aging more precisely. Our crystal structures of a model enzyme E. coli ß-gal mutant (E537Q) complexed with each probe further revealed the structural basis for probe recognition.


Assuntos
Corantes Fluorescentes/química , beta-Galactosidase/química , Senescência Celular , Escherichia coli/enzimologia , Corantes Fluorescentes/síntese química , Mutação , beta-Galactosidase/genética , beta-Galactosidase/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...