当前位置： SCI文献检索 > ACS Chemical Biology期刊下所有文献 > A Fluorescent Hsp90 Probe Demonstrates the Unique Association between Extracellular Hsp90 and Malignancy in Vivo.

A Fluorescent Hsp90 Probe Demonstrates the Unique Association between Extracellular Hsp90 and Malignancy in Vivo.

Abstract：

:Extracellular expression of heat shock protein 90 (eHsp90) by tumor cells is correlated with malignancy. Development of small molecule probes that can detect eHsp90 in vivo may therefore have utility in the early detection of malignancy. We synthesized a cell impermeable far-red fluorophore-tagged Hsp90 inhibitor to target eHsp90 in vivo. High resolution confocal and lattice light sheet microscopy show that probe-bound eHsp90 accumulates in punctate structures on the plasma membrane of breast tumor cells and is actively internalized. The extent of internalization correlates with tumor cell aggressiveness, and this process can be induced in benign cells by overexpressing p110HER2. Whole body cryoslicing, imaging, and histology of flank and spontaneous tumor-bearing mice strongly suggests that eHsp90 expression and internalization is a phenomenon unique to tumor cells in vivo and may provide an "Achilles heel" for the early diagnosis of metastatic disease and targeted drug delivery.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Crowe LB,Hughes PF,Alcorta DA,Osada T,Smith AP,Totzke J,Loiselle DR,Lutz ID,Gargesha M,Roy D,Roques J,Darr D,Lyerly HK,Spector NL,Haystead TAJ

doi

10.1021/acschembio.7b00006

subject

Has Abstract

pub_date

2017-04-21 00:00:00

pages

1047-1055

issue

4

eissn

1554-8929

issn

1554-8937

journal_volume

12

pub_type

杂志文章

相关文献

ACS Chemical Biology文献大全
  • Chemical probes of surface layer biogenesis in Clostridium difficile.

    abstract：:Clostridium difficile, a leading cause of hospital-acquired infection, possesses a dense surface layer (S-layer) that mediates host-pathogen interactions. The key structural components of the S-layer result from proteolytic cleavage of a precursor protein, SlpA, into high- and low-molecular-weight components. Here we ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb9002859

    authors： Dang TH,de la Riva L,Fagan RP,Storck EM,Heal WP,Janoir C,Fairweather NF,Tate EW

    更新日期：2010-03-19 00:00:00

  • How ATP-Competitive Inhibitors Allosterically Modulate Tyrosine Kinases That Contain a Src-like Regulatory Architecture.

    abstract：:Small molecule kinase inhibitors that stabilize distinct ATP binding site conformations can differentially modulate the global conformation of Src-family kinases (SFKs). However, it is unclear which specific ATP binding site contacts are responsible for modulating the global conformation of SFKs and whether these inhi...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.0c00429

    authors： Fang L,Vilas-Boas J,Chakraborty S,Potter ZE,Register AC,Seeliger MA,Maly DJ

    更新日期：2020-07-17 00:00:00

  • Structure-guided functional characterization of enediyne self-sacrifice resistance proteins, CalU16 and CalU19.

    abstract：:Calicheamicin γ1I (1) is an enediyne antitumor compound produced by Micromonospora echinospora spp. calichensis, and its biosynthetic gene cluster has been previously reported. Despite extensive analysis and biochemical study, several genes in the biosynthetic gene cluster of 1 remain functionally unassigned. Using a ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb500327m

    authors： Elshahawi SI,Ramelot TA,Seetharaman J,Chen J,Singh S,Yang Y,Pederson K,Kharel MK,Xiao R,Lew S,Yennamalli RM,Miller MD,Wang F,Tong L,Montelione GT,Kennedy MA,Bingman CA,Zhu H,Phillips GN Jr,Thorson JS

    更新日期：2014-10-17 00:00:00

  • Proposed Mode of Binding and Action of Positive Allosteric Modulators at Opioid Receptors.

    abstract：:Available crystal structures of opioid receptors provide a high-resolution picture of ligand binding at the primary ("orthosteric") site, that is, the site targeted by endogenous ligands. Recently, positive allosteric modulators of opioid receptors have also been discovered, but their modes of binding and action remai...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00712

    authors： Shang Y,Yeatman HR,Provasi D,Alt A,Christopoulos A,Canals M,Filizola M

    更新日期：2016-05-20 00:00:00

  • Esterase-Triggered Self-Immolative Thiocarbamates Provide Insights into COS Cytotoxicity.

    abstract：:Hydrogen sulfide (H2S) is an important gasotransmitter and biomolecule, and many synthetic small-molecule H2S donors have been developed for H2S-related research. One important class of triggerable H2S donors is self-immolative thiocarbamates, which function by releasing carbonyl sulfide (COS), which is rapidly conver...

    journal_title：ACS chemical biology

    pub_type： 信件

    doi：10.1021/acschembio.8b00981

    authors： Levinn CM,Steiger AK,Pluth MD

    更新日期：2019-02-15 00:00:00

  • Steric restrictions of RISC in RNA interference identified with size-expanded RNA nucleobases.

    abstract：:Understanding the interactions between small interfering RNAs (siRNAs) and the RNA-induced silencing complex (RISC), the key protein complex of RNA interference (RNAi), is of great importance to the development of siRNAs with improved biological and potentially therapeutic function. Although various chemically modifie...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb300174c

    authors： Hernández AR,Peterson LW,Kool ET

    更新日期：2012-08-17 00:00:00

  • Heparinoids activate a protease, secreted by mucosa and tumors, via tethering supplemented by allostery.

    abstract：:Activation by glycosaminoglycans (GAGs) is an emerging trend among extracellular proteases important in disease. ProMMP-7, the zymogen of a matrix metalloproteinase secreted by mucosal epithelial and tumor cells, is activated at their surfaces by sulfated GAGs, but how? ProMMP-7 is activated in trans by representative...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb400898t

    authors： Fulcher YG,Sanganna Gari RR,Frey NC,Zhang F,Linhardt RJ,King GM,Van Doren SR

    更新日期：2014-04-18 00:00:00

  • Bioactivity-HiTES Unveils Cryptic Antibiotics Encoded in Actinomycete Bacteria.

    abstract：:Bacteria harbor an immense reservoir of potentially new and therapeutic small molecules in the form of "silent" biosynthetic gene clusters (BGCs). These BGCs can be identified bioinformatically but are sparingly expressed under normal laboratory growth conditions, or not at all, and therefore do not produce significan...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.9b00049

    authors： Moon K,Xu F,Zhang C,Seyedsayamdost MR

    更新日期：2019-04-19 00:00:00

  • Small Molecule Targeting of a MicroRNA Associated with Hepatocellular Carcinoma.

    abstract：:Development of precision therapeutics is of immense interest, particularly as applied to the treatment of cancer. By analyzing the preferred cellular RNA targets of small molecules, we discovered that 5"-azido neomycin B binds the Drosha processing site in the microRNA (miR)-525 precursor. MiR-525 confers invasive pro...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00615

    authors： Childs-Disney JL,Disney MD

    更新日期：2016-02-19 00:00:00

  • Price for Opening the Transient Specificity Pocket in Human Aldose Reductase upon Ligand Binding: Structural, Thermodynamic, Kinetic, and Computational Analysis.

    abstract：:Insights into the thermodynamic and kinetic signature of the transient opening of a protein-binding pocket resulting from accommodation of suitable substituents attached to a given parent ligand scaffold are presented. As a target, we selected human aldose reductase, an enzyme involved in the development of late-stage...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00062

    authors： Rechlin C,Scheer F,Terwesten F,Wulsdorf T,Pol E,Fridh V,Toth P,Diederich WE,Heine A,Klebe G

    更新日期：2017-05-19 00:00:00

  • Probing enzymes late in the trypanosomal glycosylphosphatidylinositol biosynthetic pathway with synthetic glycosylphosphatidylinositol analogues.

    abstract：:Glycosylphosphatidylinositol (GPI)-anchored proteins are abundant in the protozoan parasite Trypanosoma brucei, the causative agent of African sleeping sickness in humans and the related disease Nagana in cattle, and disruption of GPI biosynthesis is genetically and chemically validated as a drug target. Here, we exam...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb800143w

    authors： Urbaniak MD,Yashunsky DV,Crossman A,Nikolaev AV,Ferguson MA

    更新日期：2008-10-17 00:00:00

  • A biosynthetic strategy for re-engineering the Staphylococcus aureus cell wall with non-native small molecules.

    abstract：:Staphylococcus aureus (S. aureus) is a Gram-positive bacterial pathogen that has emerged as a major public health threat. Here we report that the cell wall of S. aureus can be covalently re-engineered to contain non-native small molecules. This process makes use of endogenous levels of the bacterial enzyme sortase A (...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb100195d

    authors： Nelson JW,Chamessian AG,McEnaney PJ,Murelli RP,Kazmierczak BI,Spiegel DA

    更新日期：2010-12-17 00:00:00

  • Ebselen: Mechanisms of Glutamate Dehydrogenase and Glutaminase Enzyme Inhibition.

    abstract：:Ebselen modulates target proteins through redox reactions with selenocysteine/cysteine residues, or through binding to the zinc finger domains. However, a recent contradiction in ebselen inhibition of kidney type glutaminase (KGA) stimulated our interest in investigating its inhibition mechanism with glutamate dehydro...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00728

    authors： Yu Y,Jin Y,Zhou J,Ruan H,Zhao H,Lu S,Zhang Y,Li D,Ji X,Ruan BH

    更新日期：2017-12-15 00:00:00

  • Surprising Non-Additivity of Methyl Groups in Drug-Kinase Interaction.

    abstract：:Drug optimization is guided by biophysical methods with increasing popularity. In the context of lead structure modifications, the introduction of methyl groups is a simple but potentially powerful approach. Hence, it is crucial to systematically investigate the influence of ligand methylation on biophysical character...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.9b00476

    authors： Wienen-Schmidt B,Schmidt D,Gerber HD,Heine A,Gohlke H,Klebe G

    更新日期：2019-12-20 00:00:00

  • Structural Chemistry of Human RNA Methyltransferases.

    abstract：:RNA methyltransferases (RNMTs) play important roles in RNA stability, splicing, and epigenetic mechanisms. They constitute a promising target class that is underexplored by the medicinal chemistry community. Information of relevance to drug design can be extracted from the rich structural coverage of human RNMTs. In t...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00781

    authors： Schapira M

    更新日期：2016-03-18 00:00:00

  • Xanthohumol impairs autophagosome maturation through direct inhibition of valosin-containing protein.

    abstract：:Autophagy is a bulk, nonspecific protein degradation pathway that is involved in the pathogenesis of cancer and neurodegenerative disease. Here, we observed that xanthohumol (XN), a prenylated chalcone present in hops (Humulus lupulus L.) and beer, modulates autophagy. By using XN-immobilized beads, valosin-containing...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb200492h

    authors： Sasazawa Y,Kanagaki S,Tashiro E,Nogawa T,Muroi M,Kondoh Y,Osada H,Imoto M

    更新日期：2012-05-18 00:00:00

  • Small molecule signaling in Caenorhabditis elegans.

    abstract：:Whereas the C. elegans genome was sequenced many years ago, the role of small molecule signals in its biology is still poorly understood. A recent publication reports the identification of two steroidal signaling molecules that regulate C. elegans reproductive development and dauer diapause via the nuclear receptor DA...

    journal_title：ACS chemical biology

    pub_type： 杂志文章,评审

    doi：10.1021/cb600173t

    authors： Schroeder FC

    更新日期：2006-05-23 00:00:00

  • An unbiased approach to identify endogenous substrates of "histone" deacetylase 8.

    abstract：:Despite being extensively characterized structurally and biochemically, the functional role of histone deacetylase 8 (HDAC8) has remained largely obscure due in part to a lack of known cellular substrates. Herein, we describe an unbiased approach using chemical tools in conjunction with sophisticated proteomics method...

    journal_title：ACS chemical biology

    pub_type： 信件

    doi：10.1021/cb500492r

    authors： Olson DE,Udeshi ND,Wolfson NA,Pitcairn CA,Sullivan ED,Jaffe JD,Svinkina T,Natoli T,Lu X,Paulk J,McCarren P,Wagner FF,Barker D,Howe E,Lazzaro F,Gale JP,Zhang YL,Subramanian A,Fierke CA,Carr SA,Holson EB

    更新日期：2014-10-17 00:00:00

  • Construction of a rhythm transfer system that mimics the cellular clock.

    abstract：:Creation of an artificial oscillating gene expression system is one of the most challenging issues in synthetic biology. Here, we constructed a simple system to manipulate gene expression patterns to be circadian, reflecting the intrinsic cellular clock, by fusing a core clock protein, BMAL1 or CLOCK, with a zinc fing...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb300432s

    authors： Imanishi M,Yamamoto K,Yamada H,Hirose Y,Okamura H,Futaki S

    更新日期：2012-11-16 00:00:00

  • Small-molecule screening: advances in microarraying and cell-imaging technologies.

    abstract：:Cell-permeable small molecules can be used to modulate protein function selectively, rapidly, reversibly, and conditionally with temporal and quantitative control in biological systems. The identification of these chemical probes can require the screening of large numbers of small molecules. With the advent of new tec...

    journal_title：ACS chemical biology

    pub_type： 杂志文章,评审

    doi：10.1021/cb600321j

    authors： Nicholson RL,Welch M,Ladlow M,Spring DR

    更新日期：2007-01-23 00:00:00

  • High Throughput Screen Identifies Small Molecule Effectors That Modulate Thin Filament Activation in Cardiac Muscle.

    abstract：:Current therapeutic interventions for both heart disease and heart failure are largely insufficient and associated with undesired side effects. Biomedical research has emphasized the role of sarcomeric protein function for the normal performance and energy efficiency of the heart, suggesting that directly targeting th...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.0c00908

    authors： Parijat P,Kondacs L,Alexandrovich A,Gautel M,Cobb AJA,Kampourakis T

    更新日期：2021-01-15 00:00:00

  • Characterization of a Prenyltransferase for Iso-A82775C Biosynthesis and Generation of New Congeners of Chloropestolides.

    abstract：:Chloropupukeananin and chloropestolides are novel metabolites of the plant endophyte Pestalotiopsis fici, showing antimicrobial, antitumor, and anti-HIV activities. Their highly complex and unique skeletons were generated from the coisolated pestheic acid (1) and iso-A82775C (10) based on our previous studies. Here, w...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b01059

    authors： Pan Y,Liu L,Guan F,Li E,Jin J,Li J,Che Y,Liu G

    更新日期：2018-03-16 00:00:00

  • Development of a highly selective c-Src kinase inhibitor.

    abstract：:Generating highly selective probes to interrogate protein kinase function in biological studies remains a challenge, and new strategies are required. Herein, we describe the development of the first highly selective and cell-permeable inhibitor of c-Src, a key signaling kinase in cancer. Our strategy involves extensio...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb300172e

    authors： Brandvold KR,Steffey ME,Fox CC,Soellner MB

    更新日期：2012-08-17 00:00:00

  • Characterization of Sviceucin from Streptomyces Provides Insight into Enzyme Exchangeability and Disulfide Bond Formation in Lasso Peptides.

    abstract：:Lasso peptides are bacterial ribosomally synthesized and post-translationally modified peptides. They have sparked increasing interest in peptide-based drug development because of their compact, interlocked structure, which offers superior stability and protein-binding capacity. Disulfide bond-containing lasso peptide...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00584

    authors： Li Y,Ducasse R,Zirah S,Blond A,Goulard C,Lescop E,Giraud C,Hartke A,Guittet E,Pernodet JL,Rebuffat S

    更新日期：2015-11-20 00:00:00

  • Cytochrome c Reduction by H2S Potentiates Sulfide Signaling.

    abstract：:Hydrogen sulfide (H2S) is an endogenously produced gas that is toxic at high concentrations. It is eliminated by a dedicated mitochondrial sulfide oxidation pathway, which connects to the electron transfer chain at the level of complex III. Direct reduction of cytochrome c (Cyt C) by H2S has been reported previously b...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.8b00463

    authors： Vitvitsky V,Miljkovic JL,Bostelaar T,Adhikari B,Yadav PK,Steiger AK,Torregrossa R,Pluth MD,Whiteman M,Banerjee R,Filipovic MR

    更新日期：2018-08-17 00:00:00

  • Isoxazole Alters Metabolites and Gene Expression, Decreasing Proliferation and Promoting a Neuroendocrine Phenotype in β-Cells.

    abstract：:Novel strategies are needed to modulate β-cell differentiation and function as potential β-cell replacement or restorative therapies for diabetes. We previously demonstrated that small molecules based on the isoxazole scaffold drive neuroendocrine phenotypes. The nature of the effects of isoxazole compounds on β-cells...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00993

    authors： Kalwat MA,Huang Z,Wichaidit C,McGlynn K,Earnest S,Savoia C,Dioum EM,Schneider JW,Hutchison MR,Cobb MH

    更新日期：2016-04-15 00:00:00

  • Inhibition of angiogenesis by the antifungal drug itraconazole.

    abstract：:Angiogenesis, the formation of new blood vessels, is implicated in a number of important human diseases, including cancer, diabetic retinopathy, and rheumatoid arthritis. To identify clinically useful angiogenesis inhibitors, we assembled and screened a library of mostly Food and Drug Administration-approved drugs for...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb600362d

    authors： Chong CR,Xu J,Lu J,Bhat S,Sullivan DJ Jr,Liu JO

    更新日期：2007-04-24 00:00:00

  • Small molecule inhibitors of bromodomain-acetyl-lysine interactions.

    abstract：:Bromodomains are protein modules that bind to acetylated lysine residues. Their interaction with histone proteins suggests that they function as "readers" of histone lysine acetylation, a component of the proposed "histone code". Bromodomain-containing proteins are often found as components of larger protein complexes...

    journal_title：ACS chemical biology

    pub_type： 杂志文章,评审

    doi：10.1021/cb500996u

    authors： Brand M,Measures AR,Wilson BG,Cortopassi WA,Alexander R,Höss M,Hewings DS,Rooney TP,Paton RS,Conway SJ

    更新日期：2015-01-16 00:00:00

  • Furoxan Nitric Oxide Donors Disperse Pseudomonas aeruginosa Biofilms, Accelerate Growth, and Repress Pyoverdine Production.

    abstract：:The use of nitric oxide (NO) as a signal for biofilm dispersal has been shown to increase the susceptibility of many biofilms to antibiotics, promoting their eradication. The delivery of NO to biofilms can be achieved by using NO donors with different kinetics and properties of NO release that can influence their effi...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00256

    authors： Poh WH,Barraud N,Guglielmo S,Lazzarato L,Rolando B,Fruttero R,Rice SA

    更新日期：2017-08-18 00:00:00

  • Small Molecule Inhibition of miR-544 Biogenesis Disrupts Adaptive Responses to Hypoxia by Modulating ATM-mTOR Signaling.

    abstract：:Hypoxia induces a complex circuit of gene expression that drives tumor progression and increases drug resistance. Defining these changes allows for an understanding of how hypoxia alters tumor biology and informs design of lead therapeutics. We probed the role of microRNA-544 (miR-544), which silences mammalian target...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00265

    authors： Haga CL,Velagapudi SP,Strivelli JR,Yang WY,Disney MD,Phinney DG

    更新日期：2015-10-16 00:00:00