abstract：:The translation of functionally active natural products into fully synthetic small-molecule mimetics has remained an important process in medicinal chemistry. We recently discovered that the terpene natural product nimbolide can be utilized as a covalent recruiter of the E3 ubiquitin ligase RNF114 for use in targeted ...

journal_title：Cell chemical biology

authors： Luo M,Spradlin JN,Boike L,Tong B,Brittain SM,McKenna JM,Tallarico JA,Schirle M,Maimone TJ,Nomura DK

更新日期：2021-01-22 00:00:00

abstract：:Despite widespread interest for understanding how modified bases have evolved their contemporary functions, limited experimental evidence exists for measuring how close an organism is to accidentally creating a new, modified base within the framework of its existing genome. Here, we describe the biochemical and struct...

journal_title：Cell chemical biology

authors： Wang T,Kohli RM

更新日期：2021-01-21 00:00:00

abstract：:The accumulation of α-synuclein amyloid fibrils in the brain is linked to Parkinson's disease and other synucleinopathies. The intermediate species in the early aggregation phase of α-synuclein are involved in the emergence of amyloid toxicity and considered to be the most neurotoxic. The N-terminal region flanking th...

journal_title：Cell chemical biology

authors： Liang Z,Chan HYE,Lee MM,Chan MK

更新日期：2021-01-06 00:00:00

abstract：:Interfacial inhibitors exert their biological effects through co-association with two macromolecules. The pateamine A (PatA) class of molecules function by stabilizing eukaryotic initiation factor (eIF) 4A RNA helicase onto RNA, resulting in translation initiation inhibition. Here, we present the crystal structure of ...

journal_title：Cell chemical biology

authors： Naineni SK,Liang J,Hull K,Cencic R,Zhu M,Northcote P,Teesdale-Spittle P,Romo D,Nagar B,Pelletier J

更新日期：2021-01-05 00:00:00

abstract：:H2S-producing enzymes in bacteria have been shown to be closely engaged in the process of microbial survival and antibiotic resistance. However, no inhibitors have been discovered for these enzymes, e.g., 3-mercaptopyruvate sulfurtransferase (MST). In the present study, we identified several classes of inhibitors for ...

journal_title：Cell chemical biology

authors： Croppi G,Zhou Y,Yang R,Bian Y,Zhao M,Hu Y,Ruan BH,Yu J,Wu F

更新日期：2020-12-17 00:00:00

abstract：:Tumor suppressor genes represent a major class of oncogenic drivers. However, direct targeting of loss-of-function tumor suppressors remains challenging. To address this gap, we explored a variant-directed chemical biology approach to reverse the lost function of tumor suppressors using SMAD4 as an example. SMAD4, a c...

journal_title：Cell chemical biology

authors： Tang C,Mo X,Niu Q,Wahafu A,Yang X,Qui M,Ivanov AA,Du Y,Fu H

更新日期：2020-12-04 00:00:00

abstract：:Optically controlled chemical reagents, termed "photopharmaceuticals," are powerful tools for precise spatiotemporal control of proteins particularly when genetic methods, such as knockouts or optogenetics are not viable options. However, current photopharmaceutical scaffolds, such as azobenzenes are intolerant of GFP...

journal_title：Cell chemical biology

authors： Gao L,Meiring JCM,Kraus Y,Wranik M,Weinert T,Pritzl SD,Bingham R,Ntouliou E,Jansen KI,Olieric N,Standfuss J,Kapitein LC,Lohmüller T,Ahlfeld J,Akhmanova A,Steinmetz MO,Thorn-Seshold O

更新日期：2020-11-27 00:00:00

abstract：:The promise of phenotypic screening resides in its track record of novel biology and first-in-class therapies. However, challenges stemming from major differences between target-based and phenotypic screening do exist. These challenges prompted us to rethink the critical stage of hit triage and validation on the road ...

journal_title：Cell chemical biology

authors： Vincent F,Loria PM,Weston AD,Steppan CM,Doyonnas R,Wang YM,Rockwell KL,Peakman MC

更新日期：2020-11-19 00:00:00

abstract：:Activation of innate immune signaling in the tumor microenvironment is central to a successful anti-tumor immune response, and it is in large part mediated by cytosolic double-stranded DNA sensing. Here, Carozza et al. (2020b) report potent and selective inhibitors of ENPP1, a negative regulator of innate immune signa...

journal_title：Cell chemical biology

authors： Cogan D,Bakhoum SF

更新日期：2020-11-19 00:00:00

abstract：:The natural product cepafungin I was recently reported to be one of the most potent covalent inhibitors of the 20S proteasome core particle through a series of in vitro activity assays. Here, we report a short chemoenzymatic total synthesis of cepafungin I featuring the use of a regioselective enzymatic oxidation to p...

journal_title：Cell chemical biology

authors： Amatuni A,Shuster A,Adibekian A,Renata H

更新日期：2020-10-15 00:00:00

abstract：:Cryptochrome 1 (CRY1) and CRY2 are core regulators of the circadian clock, and the development of isoform-selective modulators is important for the elucidation of their redundant and distinct functions. Here, we report the identification and functional characterization of a small-molecule modulator of the mammalian ci...

journal_title：Cell chemical biology

authors： Miller S,Aikawa Y,Sugiyama A,Nagai Y,Hara A,Oshima T,Amaike K,Kay SA,Itami K,Hirota T

更新日期：2020-09-17 00:00:00

abstract：:ATP is an important energy metabolite and allosteric signal in health and disease. ATP-interacting proteins, such as P2 receptors, control inflammation, cell death, migration, and wound healing. However, identification of allosteric ATP sites remains challenging, and our current inventory of ATP-controlled pathways is...

journal_title：Cell chemical biology

authors： Jelcic M,Wang K,Hui KL,Cai XC,Enyedi B,Luo M,Niethammer P

更新日期：2020-08-20 00:00:00

abstract：:The unique photophysical properties of lanthanides, such as europium, terbium, and ytterbium, make them versatile molecular probes of biological systems. In particular, their long-lived photoluminescence, narrow bandwidth emissions, and large Stokes shifts enable experiments that are infeasible with organic fluorophor...

journal_title：Cell chemical biology

authors： Cho U,Chen JK

更新日期：2020-08-20 00:00:00

abstract：:The engineered ascorbate peroxidase (APEX) is a powerful tool for the proximity-dependent labeling of proteins and RNAs in live cells. Although widely use in mammalian cells, APEX applications in microorganisms have been hampered by the poor labeling efficiency of its biotin-phenol (BP) substrate. In this study, we so...

journal_title：Cell chemical biology

authors： Li Y,Tian C,Liu K,Zhou Y,Yang J,Zou P

更新日期：2020-07-16 00:00:00

abstract：:Infections with Salmonella enterica pose a challenge for antibiotic treatment. In this issue of Cell Chemical Biology, Tsai et al. use a chemical genomics approach to identify dephostatin as an inhibitor of intracellular Salmonella virulence in vitro and in vivo by targeting the two-component systems SsrA-SsrB and Pmr...

journal_title：Cell chemical biology

authors： Lee MH,Nuccio SP,Raffatellu M

更新日期：2020-07-16 00:00:00

abstract：:In this issue of Cell Chemical Biology, Harvey et al. (2020) identify 4E14, a sulfhydryl-containing N-acetyltryptophan analog that selectively disrupts binding to the previously undruggable anti-apoptotic BCL2 paralog BFL1, and elucidate a BFL1 conformational change that facilitates 4E14 interaction. These results pro...

journal_title：Cell chemical biology

authors： Dai H,Meng XW,Kaufmann SH

更新日期：2020-06-18 00:00:00

abstract：:Pharmacophore-focused chemical libraries are continuously being created in drug discovery programs, yet screening assays to maximize the usage of such libraries are not fully explored. Here, we report a chemical proteomics approach to reutilizing a focused chemical library of 1,800 indole-containing molecules for disc...

journal_title：Cell chemical biology

authors： Punzalan LL,Jiang L,Mao D,Mahapatra AD,Sato S,Takemoto Y,Tsujimura M,Kusamori K,Nishikawa M,Zhou L,Uesugi M

更新日期：2020-06-18 00:00:00

abstract：:Interferon-induced transmembrane protein 3 (IFITM3) is a key interferon effector that broadly prevents infection by diverse viruses. However, the cellular factors that control IFITM3 homeostasis and antiviral activity have not been fully elucidated. Using site-specific photo-crosslinking and quantitative proteomic ana...

journal_title：Cell chemical biology

authors： Wu X,Spence JS,Das T,Yuan X,Chen C,Zhang Y,Li Y,Sun Y,Chandran K,Hang HC,Peng T

更新日期：2020-05-21 00:00:00

abstract：:Acyl-coenzyme A (CoA)/protein interactions are essential for life. Despite this importance, their global scope and selectivity remains undefined. Here, we describe CATNIP (CoA/AcetylTraNsferase Interaction Profiling), a chemoproteomic platform for the high-throughput analysis of acyl-CoA/protein interactions in endoge...

journal_title：Cell chemical biology

authors： Levy MJ,Montgomery DC,Sardiu ME,Montano JL,Bergholtz SE,Nance KD,Thorpe AL,Fox SD,Lin Q,Andresson T,Florens L,Washburn MP,Meier JL

更新日期：2020-03-19 00:00:00

abstract：:Polo-like kinase 1 has hundreds of substrates and multiple functions that operate within the ∼60 min of mitosis. Herein, we describe a chemical-genetic system that allows particular substrates to be "toggled" into or out of chemical control using engineered phosphoacceptor selectivity. Biochemical assays and phosphopr...

journal_title：Cell chemical biology

authors： Johnson JM,Hebert AS,Drane QH,Lera RF,Wan J,Weaver BA,Coon JJ,Burkard ME

更新日期：2020-03-19 00:00:00

abstract：:The rapid emergence of extensively drug-resistant A. baumannii has posed a major threat to global public health, emphasizing the desperate need for novel therapeutic strategies. We report the development of a highly efficient genome-engineering platform in A. baumannii by coupling a Cas9 nuclease-mediated genome cleav...

journal_title：Cell chemical biology

authors： Wang Y,Wang Z,Chen Y,Hua X,Yu Y,Ji Q

更新日期：2019-12-19 00:00:00

abstract：:Lethal small molecules are useful probes to discover and characterize novel cell death pathways and biochemical mechanisms. Here we report that the synthetic oxime-containing small molecule caspase-independent lethal 56 (CIL56) induces an unconventional form of nonapoptotic cell death distinct from necroptosis, ferrop...

journal_title：Cell chemical biology

authors： Ko PJ,Woodrow C,Dubreuil MM,Martin BR,Skouta R,Bassik MC,Dixon SJ

更新日期：2019-12-19 00:00:00

abstract：:In this issue of Cell Chemical Biology, Shah et al. (2019) report an in vitro, high-throughput assay that predicts the ability of compounds to suppress peroxidation of phospholipids. This approach provides a way to design and optimize targeted antioxidants that suppress specific oxidative event in cells, potentially o...

journal_title：Cell chemical biology

authors： Stockwell BR

更新日期：2019-11-21 00:00:00

abstract：:Because small-molecule activators of adenylyl cyclases (AC) affect ACs cell-wide, it is challenging to explore the signaling consequences of AC activity emanating from specific intracellular compartments. We explored this issue using a series of engineered, optogenetic, spatially restricted, photoactivable adenylyl cy...

journal_title：Cell chemical biology

authors： O'Banion CP,Vickerman BM,Haar L,Lawrence DS

更新日期：2019-10-17 00:00:00

abstract：:Pyridoxal 5'-phosphate (PLP) is a versatile cofactor that catalyzes a plethora of chemical transformations within a cell. Although many human PLP-dependent enzymes (PLP-DEs) with crucial physiological and pathological roles are known, a global method enabling their cellular profiling is lacking. Here, we demonstrate t...

journal_title：Cell chemical biology

authors： Fux A,Pfanzelt M,Kirsch VC,Hoegl A,Sieber SA

更新日期：2019-10-17 00:00:00

abstract：:A protein-fragment complementation assay (PCA) for detecting and localizing intracellular protein-protein interactions (PPIs) was built by bisection of miniSOG, a fluorescent flavoprotein derived from the light, oxygen, voltage (LOV)-2 domain of Arabidopsis phototropin. When brought together by interacting proteins, t...

journal_title：Cell chemical biology

authors： Boassa D,Lemieux SP,Lev-Ram V,Hu J,Xiong Q,Phan S,Mackey M,Ramachandra R,Peace RE,Adams SR,Ellisman MH,Ngo JT

更新日期：2019-10-17 00:00:00

abstract：:In this issue of Cell Chemical Biology, Radlinski et al. (2019) identify Pseudomonas-derived rhamnolipids that potentiate aminoglycoside antibiotics in the eradication of antibiotic-tolerant bacterial phenotypes. Microbial physiological and mechanistic studies indicate that rhamnolipids permeabilize S. aureus membrane...

journal_title：Cell chemical biology

authors： Yarlagadda V,Wright GD

更新日期：2019-10-17 00:00:00

abstract：:Recent advances in induced pluripotent stem cell technologies and phenotypic screening shape the future of bioactive small-molecule discovery. In this review we analyze the impact of small-molecule phenotypic screens on drug discovery as well as on the investigation of human development and disease biology. We further...

journal_title：Cell chemical biology

authors： Friese A,Ursu A,Hochheimer A,Schöler HR,Waldmann H,Bruder JM

更新日期：2019-08-15 00:00:00

abstract：:Small-molecule targeted recruitment of nucleases to RNA is a powerful method to affect RNA biology. Inforna, a sequence-based design approach to target RNA, enables the design of small molecules that bind to and cleave RNA in a selective and substoichiometric manner. Here, we investigate the ability of RNA-targeted de...

journal_title：Cell chemical biology

authors： Costales MG,Suresh B,Vishnu K,Disney MD

更新日期：2019-08-15 00:00:00

abstract：:Increased telomerase activity is associated with malignancy and poor prognosis in human cancer, but the development of targeted agents has not yet provided clinical benefit. Here we report that, instead of targeting the telomerase enzyme directly, small molecules that bind to the G-hairpin of the hTERT G-quadruplex-fo...

journal_title：Cell chemical biology

authors： Song JH,Kang HJ,Luevano LA,Gokhale V,Wu K,Pandey R,Sherry Chow HH,Hurley LH,Kraft AS

更新日期：2019-08-15 00:00:00

abstract：:Disorders of bone healing and remodeling are indications with an unmet need for effective pharmacological modulators. We used a high-throughput screen to identify activators of the bone marker alkaline phosphatase (ALP), and discovered 6,8-dimethyl-3-(4-phenyl-1H-imidazol-5-yl)quinolin-2(1H)-one (DIPQUO). DIPQUO marke...

journal_title：Cell chemical biology

authors： Cook B,Rafiq R,Lee H,Banks KM,El-Debs M,Chiaravalli J,Glickman JF,Das BC,Chen S,Evans T

更新日期：2019-07-18 00:00:00

abstract：:In this issue of Cell Chemical Biology, Cook et al. (2019) report a new small-molecule activator that enhances osteogenesis and skeletal regeneration in developmental and adult animal models, respectively. This discovery has therapeutic potential for healing following traumatic bone injury, as well as bone remodeling ...

journal_title：Cell chemical biology

authors： Chang JW,Moellering RE

更新日期：2019-07-18 00:00:00

abstract：:In this issue of Cell Chemical Biology, Olson et al. (2019) develop the first selective CDK7 irreversible inhibitor. Elegant cell-based studies using a CDK7 mutant that is not covalently engaged by the probe helped decipher the effects of inhibiting the kinase on the cell cycle and gene transcription. ...

journal_title：Cell chemical biology

authors： Jones LH

更新日期：2019-06-20 00:00:00

abstract：:Contrary to the classic model of protein kinase A (PKA) residing outside of the nucleus, we identify a nuclear signaling complex that consists of AKAP95, PKA, and PDE4D5 and show that it forms a functional cyclic AMP (cAMP) signaling microdomain. Locally generated cAMP can accumulate within the vicinity of this comple...

journal_title：Cell chemical biology

authors： Clister T,Greenwald EC,Baillie GS,Zhang J

更新日期：2019-06-20 00:00:00

abstract：:Non-ribosomal peptides (NRPs) are biosynthesized on non-ribosomal peptides synthetase (NRPS) complexes, of which a C-terminal releasing domain commonly offloads the products. Interestingly, a dedicated releasing domain is absent in surugamides (SGM) NRPS, which directs the biosynthesis of cyclic octapeptides, SGM-A to...

journal_title：Cell chemical biology

authors： Zhou Y,Lin X,Xu C,Shen Y,Wang SP,Liao H,Li L,Deng H,Lin HW

更新日期：2019-05-16 00:00:00

abstract：:While the wound healing property of the macrolide FK506 is well known, the underlying mechanism has been elusive. In this issue of Cell Chemical Biology, Peiffer et al. (2019) utilize FKBP12 ligand to demonstrate that wound healing effects of FK506 occur via activation of the BMP (bone morphogenic protein) signaling p...

journal_title：Cell chemical biology

authors： Williams CH,Hong CC

更新日期：2019-05-16 00:00:00

abstract：:Genetically encoded biosensors are useful tools for detecting the presence and levels of diverse biomolecules in living cells. However, low-abundance targets are difficult to detect because they are often unable to bind and activate enough biosensors to detect using standard microscopic imaging approaches. Here we des...

journal_title：Cell chemical biology

authors： You M,Litke JL,Wu R,Jaffrey SR

更新日期：2019-04-18 00:00:00

abstract：:Ubiquinone (UQ) is a conserved polyprenylated lipid essential to cellular respiration. Two papers, one in this issue of Cell Chemical Biology (Hajj Chehade et al., 2019) and another in Molecular Cell (Lohman et al., 2019), identify lipid-binding proteins that play crucial roles in chaperoning UQ-intermediates. ...

journal_title：Cell chemical biology

authors： Tsui HS,Clarke CF

更新日期：2019-04-18 00:00:00

abstract：:The glycan ligands recognized by Siglecs, influenza viruses, and galectins, as well as many plant lectins, are not well defined. To explore their binding to asparagine (Asn)-linked N-glycans, we synthesized a library of isomeric multiantennary N-glycans that vary in terminal non-reducing sialic acid, galactose, and N-...

journal_title：Cell chemical biology

authors： Gao C,Hanes MS,Byrd-Leotis LA,Wei M,Jia N,Kardish RJ,McKitrick TR,Steinhauer DA,Cummings RD

更新日期：2019-04-18 00:00:00

abstract：:Eicosanoids and related oxylipins are critical, small bioactive mediators of human physiology and inflammation. While ∼1,100 distinct species have been predicted to exist, to date, less than 150 of these molecules have been measured in humans, limiting our understanding of their role in human biology. Using a directed...

journal_title：Cell chemical biology

authors： Watrous JD,Niiranen TJ,Lagerborg KA,Henglin M,Xu YJ,Rong J,Sharma S,Vasan RS,Larson MG,Armando A,Mora S,Quehenberger O,Dennis EA,Cheng S,Jain M

更新日期：2019-03-21 00:00:00