Design and Application of a DNA-Encoded Macrocyclic Peptide Library.

abstract：:There is increasing concern that animal and human reproduction may be adversely affected by exposure to xenoestrogens that activate estrogen receptors. There is evidence that one such compound, Bisphenol A (BPA), also induces meiotic and mitotic aneuploidy, suggesting that these kinds of molecules may also have effect...

journal_title：ACS chemical biology

authors： George O,Bryant BK,Chinnasamy R,Corona C,Arterburn JB,Shuster CB

更新日期：2008-03-20 00:00:00

abstract：:SGK3 is a PX domain containing protein kinase activated at endosomes downstream of class 1 and 3 PI3K family members by growth factors and oncogenic mutations. SGK3 plays a key role in mediating resistance of breast cancer cells to class 1 PI3K or Akt inhibitors, by substituting for the loss of Akt activity and restor...

journal_title：ACS chemical biology

authors： Tovell H,Testa A,Zhou H,Shpiro N,Crafter C,Ciulli A,Alessi DR

更新日期：2019-09-20 00:00:00

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

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

更新日期：2008-10-17 00:00:00

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

authors： Levinn CM,Steiger AK,Pluth MD

更新日期：2019-02-15 00:00:00

abstract：:The gibberellin (GA) phytohormones are produced not only by plants but also by fungi and bacteria. Previous characterization of a cytochrome P450 (CYP)-rich GA biosynthetic operon found in many symbiotic, nitrogen-fixing rhizobia led to the elucidation of bacterial GA biosynthesis and implicated GA9 as the final produ...

journal_title：ACS chemical biology

authors： Nett RS,Contreras T,Peters RJ

更新日期：2017-04-21 00:00:00

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

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

更新日期：2019-04-19 00:00:00

abstract：:We report here an isatin derivative 45 (ID45) against coxsackievirus B3 (CVB3) replication, which was synthesized based on a high-throughput screen of a unique natural product library. ID45 showed the most potent anti-CVB3 activity among the four synthesized compounds. Treatment of cells with ID45 before or after infe...

journal_title：ACS chemical biology

authors： Zhang HM,Dai H,Hanson PJ,Li H,Guo H,Ye X,Hemida MG,Wang L,Tong Y,Qiu Y,Liu S,Wang F,Song F,Zhang B,Wang JG,Zhang LX,Yang D

更新日期：2014-04-18 00:00:00

abstract：:Fusicoccin A is a diterpene glucoside phytotoxin generated by the fungal pathogen Phomopsis amygdali that causes the plant disease constriction canker, first discovered in New Jersey peach orchards in the 1930s. Fusicoccin A is also an emerging new lead in cancer chemotherapy. The hydrocarbon precursor of fusicoccin A...

journal_title：ACS chemical biology

authors： Chen M,Chou WK,Toyomasu T,Cane DE,Christianson DW

更新日期：2016-04-15 00:00:00

abstract：:The emergence of multidrug-resistant Staphylococcus aureus strains has become a serious clinical problem. Iron is absolutely required for the bacterial growth, virulence associated with colonization, and survival from the host immune system. The FeoB protein is a major iron permease in bacterial ferrous iron transport...

journal_title：ACS chemical biology

authors： Shin M,Jin Y,Park J,Mun D,Kim SR,Payne SM,Kim KH,Kim Y

更新日期：2021-01-15 00:00:00

abstract：:Cutaneous leishmaniasis remains ignored in therapeutic drug discovery programs worldwide. This is mainly because cutaneous leishmaniasis is frequently a disease of impoverished populations in countries where funds are limited for research and patient care. However, the health burden of individuals in endemic areas man...

journal_title：ACS chemical biology

authors： Sharlow ER,Leimgruber S,Murray S,Lira A,Sciotti RJ,Hickman M,Hudson T,Leed S,Caridha D,Barrios AM,Close D,Grögl M,Lazo JS

更新日期：2014-03-21 00:00:00

abstract：:Targeting native progenitors with small molecule pharmaceuticals that direct cell fate decisions is an attractive approach for regenerative medicine. Here, we show that 3,5-disubstituted isoxazoles (Isx), stem cell-modulator small molecules originally recovered in a P19 embryonal carcinoma cell-based screen, directed ...

journal_title：ACS chemical biology

authors： Russell JL,Goetsch SC,Aguilar HR,Frantz DE,Schneider JW

更新日期：2012-06-15 00:00:00

abstract：:Mutations in the NPHP1 gene, coding for human nephrocystin-1 (NPHP1), cause the autosomal recessive disease nephronophthisis, the most common cause of end-stage renal disease in children and adolescents. The function and structure of NPHP1 are still poorly characterized. NPHP1 presents a modular structure well in keep...

journal_title：ACS chemical biology

authors： Mannella V,Quilici G,Nigro EA,Lampis M,Minici C,Degano M,Boletta A,Musco G

更新日期：2019-08-16 00:00:00

abstract：:Acute and specific sensing of diatomic gas molecules is an essential facet of biological signaling. Heme nitric oxide/oxygen binding (H-NOX) proteins are a family of gas sensors found in diverse classes of bacteria and eukaryotes. The most commonly characterized bacterial H-NOX domains are from facultative anaerobes a...

journal_title：ACS chemical biology

authors： Hespen CW,Bruegger JJ,Phillips-Piro CM,Marletta MA

更新日期：2016-08-19 00:00:00

abstract：:Protein-fragment complementation assays (PCAs) are widely used for investigating protein interactions. However, the fragments used are structurally compromised and have not been optimized nor thoroughly characterized for accurately assessing these interactions. We took advantage of the small size and bright luminescen...

journal_title：ACS chemical biology

authors： Dixon AS,Schwinn MK,Hall MP,Zimmerman K,Otto P,Lubben TH,Butler BL,Binkowski BF,Machleidt T,Kirkland TA,Wood MG,Eggers CT,Encell LP,Wood KV

更新日期：2016-02-19 00:00:00

abstract：:For the specificity of ALOX15 orthologs of different mammals, the geometry of the amino acids Phe353, Ile418, Met419, and Ile593 ("triad determinants") is important, and mutagenesis of these residues altered the reaction specificity of these enzymes. Here we expressed wild-type human ALOX5 and its F359W/A424I/N425M/A6...

journal_title：ACS chemical biology

authors： Ivanov I,Golovanov AB,Ferretti C,Canyelles-Niño M,Heydeck D,Stehling S,Lluch JM,González-Lafont À,Kühn H

更新日期：2019-12-20 00:00:00

abstract：:Peptidoglycan glycosyltransferases (PGTs), enzymes that catalyze the formation of the glycan chains of the bacterial cell wall, have tremendous potential as antibiotic targets. The moenomycins, a potent family of natural product antibiotics, are the only known active site inhibitors of the PGTs and serve as blueprints...

journal_title：ACS chemical biology

authors： Yuan Y,Fuse S,Ostash B,Sliz P,Kahne D,Walker S

更新日期：2008-07-18 00:00:00

abstract：:Post-translational modifications of histones alter chromatin structure and play key roles in gene expression and specification of cell states. Small molecules that target chromatin-modifying enzymes selectively are useful as probes and have promise as therapeutics, although very few are currently available. G9a (also ...

journal_title：ACS chemical biology

authors： Yuan Y,Wang Q,Paulk J,Kubicek S,Kemp MM,Adams DJ,Shamji AF,Wagner BK,Schreiber SL

更新日期：2012-07-20 00:00:00

abstract：:Thermodynamics and kinetics of protein-ligand binding are both important aspects for the design of novel drug molecules. Presently, thermodynamic data are collected with isothermal titration calorimetry, while kinetic data are mostly derived from surface plasmon resonance. The new method of kinITC provides both thermo...

journal_title：ACS chemical biology

authors： Glöckner S,Ngo K,Sager CP,Hüfner-Wulsdorf T,Heine A,Klebe G

更新日期：2020-03-20 00:00:00

abstract：:Elevation of reactive oxygen species (ROS) levels has been observed in many cancer cells relative to nontransformed cells, and recent reports have suggested that small-molecule enhancers of ROS may selectively kill cancer cells in various in vitro and in vivo models. We used a high-throughput screening approach to ide...

journal_title：ACS chemical biology

authors： Adams DJ,Boskovic ZV,Theriault JR,Wang AJ,Stern AM,Wagner BK,Shamji AF,Schreiber SL

更新日期：2013-05-17 00:00:00

abstract：:Enzymatic transfer of the AMP portion of ATP to substrate proteins has recently been described as an essential mechanism of bacterial infection for several pathogens. The first AMPylator to be discovered, VopS from Vibrio parahemolyticus, catalyzes the transfer of AMP onto the host GTPases Cdc42 and Rac1. Modification...

journal_title：ACS chemical biology

authors： Lewallen DM,Sreelatha A,Dharmarajan V,Madoux F,Chase P,Griffin PR,Orth K,Hodder P,Thompson PR

更新日期：2014-02-21 00:00:00

abstract：:Replacing the two Mn(2+) ions normally present in human Arginase I with Co(2+) resulted in a significantly lowered K(M) value without a concomitant reduction in k(cat). In addition, the pH dependence of the reaction was shifted from a pK(a) of 8.5 to a pK(a) of 7.5. The combination of these effects led to a 10-fold in...

journal_title：ACS chemical biology

authors： Stone EM,Glazer ES,Chantranupong L,Cherukuri P,Breece RM,Tierney DL,Curley SA,Iverson BL,Georgiou G

更新日期：2010-03-19 00:00:00

abstract：:Apicomplexan parasites, including Plasmodium falciparum and Toxoplasma gondii, the causative agents of severe malaria and toxoplasmosis, respectively, undergo several critical developmental transitions during their lifecycle. Most important for human pathogenesis is the asexual cycle, in which parasites undergo rounds...

journal_title：ACS chemical biology

authors： Howard BL,Harvey KL,Stewart RJ,Azevedo MF,Crabb BS,Jennings IG,Sanders PR,Manallack DT,Thompson PE,Tonkin CJ,Gilson PR

更新日期：2015-04-17 00:00:00

abstract：:A major risk for patients having estrogen receptor α (ERα)-positive breast cancer is the recurrence of drug-resistant metastases after initial successful treatment with endocrine therapies. Recent studies have implicated a number of activating mutations in the ligand-binding domain of ERα that stabilize the agonist co...

journal_title：ACS chemical biology

authors： Sharma A,Toy W,Guillen VS,Sharma N,Min J,Carlson KE,Mayne CG,Lin S,Sabio M,Greene G,Katzenellenbogen BS,Chandarlapaty S,Katzenellenbogen JA

更新日期：2018-12-21 00:00:00

abstract：:The anxiolytic, anticonvulsant, muscle-relaxant, and sedative-hypnotic effects of benzodiazepine site ligands are mainly elicited by allosteric modulation of GABAA receptors via their extracellular αx+/γ2- ( x = 1, 2, 3, 5) interfaces. In addition, a low affinity binding site at the homologous α+/β- interfaces was rep...

journal_title：ACS chemical biology

authors： Siebert DCB,Bampali K,Puthenkalam R,Varagic Z,Sarto-Jackson I,Scholze P,Sieghart W,Mihovilovic MD,Schnürch M,Ernst M

更新日期：2018-08-17 00:00:00

abstract：:Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology. Herein, we developed an isotope-tagged cleavable linker (isoTCL) strategy, which enabled isotopic labeling of O-GlcNAc through bioorthogonal conj...

journal_title：ACS chemical biology

authors： Qin K,Zhu Y,Qin W,Gao J,Shao X,Wang YL,Zhou W,Wang C,Chen X

更新日期：2018-08-17 00:00:00

abstract：:Phosphatases play key roles in normal physiology and diseases. Studying phosphatases has been both essential and challenging, and the application of conventional genetic and biochemical methods has led to crucial but still limited understanding of their mechanisms, substrates, and exclusive functions within highly int...

journal_title：ACS chemical biology

authors： Fahs S,Lujan P,Köhn M

更新日期：2016-11-18 00:00:00

abstract：:The steady increase in the prevalence of multidrug-resistant Staphylococcus aureus has made the search for novel antibiotics to combat this clinically important pathogen an urgent matter. In an effort to discover antibacterials with new chemical structures and mechanisms, we performed a growth inhibition screen of a s...

journal_title：ACS chemical biology

authors： Wang J,Ye X,Yang X,Cai Y,Wang S,Tang J,Sachdeva M,Qian Y,Hu W,Leeds JA,Yuan Y

更新日期：2020-07-17 00:00:00

abstract：:Synthetic compounds for controlling or creating human immunity have the potential to revolutionize disease treatment. Motivated by challenges in this arena, we report herein a strategy to target metastatic cancer cells for immune-mediated destruction by targeting the urokinase-type plasminogen activator receptor (uPAR...

journal_title：ACS chemical biology

authors： Jakobsche CE,McEnaney PJ,Zhang AX,Spiegel DA

更新日期：2012-02-17 00:00:00

abstract：:Unrelated ligands, often found in drug discovery campaigns, can bind to the same receptor, even with the same protein residues. To investigate how this might occur, and whether it might be typically possible to find unrelated ligands for the same drug target, we sought examples of topologically unrelated ligands that ...

journal_title：ACS chemical biology

authors： Pottel J,Levit A,Korczynska M,Fischer M,Shoichet BK

更新日期：2018-09-21 00:00:00

abstract：:The β-hydroxylation of l-histidine is the first step in the biosynthesis of the imidazolone base of the antifungal drug nikkomycin. The cytochrome P450 (NikQ) hydroxylates the amino acid while it is appended via a phosphopantetheine linker to the non-ribosomal peptide synthetase (NRPS) NikP1. The latter enzyme is comp...

journal_title：ACS chemical biology

authors： Wise CE,Makris TM

更新日期：2017-05-19 00:00:00