Selective irreversible inhibition of a protease by targeting a noncatalytic cysteine.

abstract：:We describe a new technology for recruiting specific proteins to RNA through selective recognition of heteroduplexes formed with chemically modified antisense oligonucleotides (ASOs). Typically, ASOs function by hybridizing to their RNA targets and blocking the binding of single-stranded RNA-binding proteins. Unexpect...

journal_title：Nature chemical biology

authors： Rigo F,Hua Y,Chun SJ,Prakash TP,Krainer AR,Bennett CF

更新日期：2012-04-15 00:00:00

abstract：:Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vi...

journal_title：Nature chemical biology

authors： Ferguson FM,Nabet B,Raghavan S,Liu Y,Leggett AL,Kuljanin M,Kalekar RL,Yang A,He S,Wang J,Ng RWS,Sulahian R,Li L,Poulin EJ,Huang L,Koren J,Dieguez-Martinez N,Espinosa S,Zeng Z,Corona CR,Vasta JD,Ohi R,Sim T,K

更新日期：2020-06-01 00:00:00

abstract：:Specific chemicals can prime the plant immune system for augmented defense. β-aminobutyric acid (BABA) is a priming agent that provides broad-spectrum disease protection. However, BABA also suppresses plant growth when applied in high doses, which has hampered its application as a crop defense activator. Here we descr...

journal_title：Nature chemical biology

authors： Luna E,van Hulten M,Zhang Y,Berkowitz O,López A,Pétriacq P,Sellwood MA,Chen B,Burrell M,van de Meene A,Pieterse CM,Flors V,Ton J

更新日期：2014-06-01 00:00:00

abstract：:Cell-permeable small molecules that inhibit their targets on fast timescales are powerful probes of cell-division mechanisms. Such inhibitors have been identified using phenotype-based screens with chemical libraries. However, the characteristics of compound libraries needed to effectively span cell-division phenotype...

journal_title：Nature chemical biology

authors： Peters U,Cherian J,Kim JH,Kwok BH,Kapoor TM

更新日期：2006-11-01 00:00:00

abstract：:Synthetic mRNA is an attractive vehicle for gene therapies because of its transient nature and improved safety profile over DNA. However, unlike DNA, broadly applicable methods to control expression from mRNA are lacking. Here we describe a platform for small-molecule-based regulation of expression from modified RNA (...

journal_title：Nature chemical biology

authors： Wagner TE,Becraft JR,Bodner K,Teague B,Zhang X,Woo A,Porter E,Alburquerque B,Dobosh B,Andries O,Sanders NN,Beal J,Densmore D,Kitada T,Weiss R

更新日期：2018-11-01 00:00:00

abstract：:A required course in communication at the graduate school level may help cure the disorder of poor scientific writing. ...

journal_title：Nature chemical biology

authors：

更新日期：2006-09-01 00:00:00

abstract：:Cysteine dioxygenase (CDO) plays an essential role in sulfur metabolism by regulating homeostatic levels of cysteine. Human CDO contains a post-translationally generated Cys93-Tyr157 cross-linked cofactor. Here, we investigated this Cys-Tyr cross-linking by incorporating unnatural tyrosines in place of Tyr157 via a ge...

journal_title：Nature chemical biology

authors： Li J,Griffith WP,Davis I,Shin I,Wang J,Li F,Wang Y,Wherritt DJ,Liu A

更新日期：2018-09-01 00:00:00

abstract：:Phenylketonuria (PKU) is characterized by phenylalanine accumulation and progressive mental retardation caused by an unknown mechanism. We demonstrate that at pathological concentrations, phenylalanine self-assembles into fibrils with amyloid-like morphology and well-ordered electron diffraction. These assemblies are ...

journal_title：Nature chemical biology

authors： Adler-Abramovich L,Vaks L,Carny O,Trudler D,Magno A,Caflisch A,Frenkel D,Gazit E

更新日期：2012-08-01 00:00:00

abstract：:Bifunctional Rel stringent factors, the most abundant class of RelA/SpoT homologs, are ribosome-associated enzymes that transfer a pyrophosphate from ATP onto the 3' of guanosine tri-/diphosphate (GTP/GDP) to synthesize the bacterial alarmone (p)ppGpp, and also catalyze the 3' pyrophosphate hydrolysis to degrade it. T...

journal_title：Nature chemical biology

authors： Tamman H,Van Nerom K,Takada H,Vandenberk N,Scholl D,Polikanov Y,Hofkens J,Talavera A,Hauryliuk V,Hendrix J,Garcia-Pino A

更新日期：2020-08-01 00:00:00

abstract：:Foldamers are sequence-specific oligomers akin to peptides, proteins and oligonucleotides that fold into well-defined three-dimensional structures. They offer the chemical biologist a broad pallet of building blocks for the construction of molecules that test and extend our understanding of protein folding and functio...

journal_title：Nature chemical biology

authors： Goodman CM,Choi S,Shandler S,DeGrado WF

更新日期：2007-05-01 00:00:00

abstract：:Methods to evolve synthetic, rather than biological, polymers could significantly expand the functional potential of polymers that emerge from in vitro evolution. Requirements for synthetic polymer evolution include (i) sequence-specific polymerization of synthetic building blocks on an amplifiable template, (ii) disp...

journal_title：Nature chemical biology

authors： Brudno Y,Birnbaum ME,Kleiner RE,Liu DR

更新日期：2010-02-01 00:00:00

abstract：:Enzymatic incorporation of a halogen atom is a common feature in the biosyntheses of more than 4,500 natural products. Halogenation of unactivated carbon centers in the biosyntheses of several compounds of nonribosomal peptide origin is carried out by a class of mononuclear nonheme iron enzymes that require alpha-keto...

journal_title：Nature chemical biology

authors： Galonić DP,Barr EW,Walsh CT,Bollinger JM Jr,Krebs C

更新日期：2007-02-01 00:00:00

abstract：:Intracellular Ca(2+) regulates numerous proteins and cellular functions and can vary substantially over submicron and submillisecond scales, so precisely localized fast detection is desirable. We have created a approximately 1-kDa biarsenical Ca(2+) indicator, called Calcium Green FlAsH (CaGF, 1), to probe [Ca(2+)] su...

journal_title：Nature chemical biology

authors： Tour O,Adams SR,Kerr RA,Meijer RM,Sejnowski TJ,Tsien RW,Tsien RY

更新日期：2007-07-01 00:00:00

abstract：:Mammals that degrade uric acid are not affected by gout or urate kidney stones. It is not fully understood how they convert uric acid into the much more soluble allantoin. Until recently, it had long been thought that urate oxidase was the only enzyme responsible for this conversion. However, detailed studies of the m...

journal_title：Nature chemical biology

authors： Ramazzina I,Folli C,Secchi A,Berni R,Percudani R

更新日期：2006-03-01 00:00:00

abstract：:Cyclin-dependent kinase 9 (CDK9), an important regulator of transcriptional elongation, is a promising target for cancer therapy, particularly for cancers driven by transcriptional dysregulation. We characterized NVP-2, a selective ATP-competitive CDK9 inhibitor, and THAL-SNS-032, a selective CDK9 degrader consisting ...

journal_title：Nature chemical biology

authors： Olson CM,Jiang B,Erb MA,Liang Y,Doctor ZM,Zhang Z,Zhang T,Kwiatkowski N,Boukhali M,Green JL,Haas W,Nomanbhoy T,Fischer ES,Young RA,Bradner JE,Winter GE,Gray NS

更新日期：2018-02-01 00:00:00

abstract：:Lysine riboswitches are bacterial RNA structures that sense the concentration of lysine and regulate the expression of lysine biosynthesis and transport genes. Members of this riboswitch class are found in the 5' untranslated region of messenger RNAs, where they form highly selective receptors for lysine. Lysine bindi...

journal_title：Nature chemical biology

authors： Blount KF,Wang JX,Lim J,Sudarsan N,Breaker RR

更新日期：2007-01-01 00:00:00

abstract：:Naturally produced polybrominated diphenyl ethers (PBDEs) pervade the marine environment and structurally resemble toxic man-made brominated flame retardants. PBDEs bioaccumulate in marine animals and are likely transferred to the human food chain. However, the biogenic basis for PBDE production in one of their most p...

journal_title：Nature chemical biology

authors： Agarwal V,Blanton JM,Podell S,Taton A,Schorn MA,Busch J,Lin Z,Schmidt EW,Jensen PR,Paul VJ,Biggs JS,Golden JW,Allen EE,Moore BS

更新日期：2017-05-01 00:00:00

abstract：:Mycobacterium tuberculosis and Yersinia pestis, the causative agents of tuberculosis and plague, respectively, are pathogens with serious ongoing impact on global public health and potential use as agents of bioterrorism. Both pathogens have iron acquisition systems based on siderophores, secreted iron-chelating compo...

journal_title：Nature chemical biology

authors： Ferreras JA,Ryu JS,Di Lello F,Tan DS,Quadri LE

更新日期：2005-06-01 00:00:00

abstract：:Targeted protein degradation via small-molecule modulation of cereblon offers vast potential for the development of new therapeutics. Cereblon-binding therapeutics carry the safety risks of thalidomide, which caused an epidemic of severe birth defects characterized by forelimb shortening or phocomelia. Here we show th...

journal_title：Nature chemical biology

authors： Matyskiela ME,Couto S,Zheng X,Lu G,Hui J,Stamp K,Drew C,Ren Y,Wang M,Carpenter A,Lee CW,Clayton T,Fang W,Lu CC,Riley M,Abdubek P,Blease K,Hartke J,Kumar G,Vessey R,Rolfe M,Hamann LG,Chamberlain PP

更新日期：2018-10-01 00:00:00

abstract：:The actin cytoskeleton supports diverse cellular processes such as endocytosis, oriented growth, adhesion and migration. The dynamic nature of the cytoskeleton, however, has made it difficult to define the roles of the many accessory molecules that modulate actin organization, especially the multifunctional adapter pr...

journal_title：Nature chemical biology

authors： Falsey RR,Marron MT,Gunaherath GM,Shirahatti N,Mahadevan D,Gunatilaka AA,Whitesell L

更新日期：2006-01-01 00:00:00

abstract：:CRISPR-Cas9 has emerged as a powerful technology that enables ready modification of the mammalian genome. The ability to modulate Cas9 activity can reduce off-target cleavage and facilitate precise genome engineering. Here we report the development of a Cas9 variant whose activity can be switched on and off in human c...

journal_title：Nature chemical biology

authors： Liu KI,Ramli MN,Woo CW,Wang Y,Zhao T,Zhang X,Yim GR,Chong BY,Gowher A,Chua MZ,Jung J,Lee JH,Tan MH

更新日期：2016-11-01 00:00:00

abstract：:Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have distinct clinical features but a common pathology--cytoplasmic inclusions rich in transactive response element DNA-binding protein of 43 kDa (TDP43). Rare TDP43 mutations cause ALS or FTD, but abnormal TDP43 levels and localization may cause di...

journal_title：Nature chemical biology

authors： Barmada SJ,Serio A,Arjun A,Bilican B,Daub A,Ando DM,Tsvetkov A,Pleiss M,Li X,Peisach D,Shaw C,Chandran S,Finkbeiner S

更新日期：2014-08-01 00:00:00

abstract：:Liver X receptors (Lxrα and Lxrβ) are ligand-dependent nuclear receptors critical for ventral midbrain neurogenesis in vivo. However, no endogenous midbrain Lxr ligand has so far been identified. Here we used LC/MS and functional assays to identify cholic acid as a new Lxr ligand. Moreover, 24(S),25-epoxycholesterol (...

journal_title：Nature chemical biology

authors： Theofilopoulos S,Wang Y,Kitambi SS,Sacchetti P,Sousa KM,Bodin K,Kirk J,Saltó C,Gustafsson M,Toledo EM,Karu K,Gustafsson JÅ,Steffensen KR,Ernfors P,Sjövall J,Griffiths WJ,Arenas E

更新日期：2013-02-01 00:00:00

abstract：:We report that simple glycoside donors can drastically shift the equilibria of glycosyltransferase-catalyzed reactions, transforming NDP-sugar formation from an endothermic to an exothermic process. To demonstrate the utility of this thermodynamic adaptability, we highlight the glycosyltransferase-catalyzed synthesis ...

journal_title：Nature chemical biology

authors： Gantt RW,Peltier-Pain P,Cournoyer WJ,Thorson JS

更新日期：2011-08-21 00:00:00

abstract：:The nematode Caenorhabditis elegans requires exogenous cholesterol to survive and its depletion leads to early developmental arrest. Thus, tight regulation of cholesterol storage and distribution within the organism is indispensable. Here, we present a novel class of C. elegans phosphorylated glycosphingolipids, phosp...

journal_title：Nature chemical biology

authors： Boland S,Schmidt U,Zagoriy V,Sampaio JL,Fritsche RF,Czerwonka R,Lübken T,Reimann J,Penkov S,Knölker HJ,Kurzchalia TV

更新日期：2017-06-01 00:00:00

abstract：:The heat shock protein 90 (Hsp90) has a critical role in malignant transformation. Whereas its ability to maintain the functional conformations of mutant and aberrant oncoproteins is established, a transformation-specific regulation of the antiapoptotic phenotype by Hsp90 is poorly understood. By using selective compo...

journal_title：Nature chemical biology

authors： Rodina A,Vilenchik M,Moulick K,Aguirre J,Kim J,Chiang A,Litz J,Clement CC,Kang Y,She Y,Wu N,Felts S,Wipf P,Massague J,Jiang X,Brodsky JL,Krystal GW,Chiosis G

更新日期：2007-08-01 00:00:00

abstract：:Trafficking and sorting of membrane-anchored Ras GTPases are regulated by partitioning between distinct membrane domains. Here, in vitro experiments and microscopic molecular theory reveal membrane curvature as a new modulator of N-Ras lipid anchor and palmitoyl chain partitioning. Membrane curvature was essential for...

journal_title：Nature chemical biology

authors： Larsen JB,Jensen MB,Bhatia VK,Pedersen SL,Bjørnholm T,Iversen L,Uline M,Szleifer I,Jensen KJ,Hatzakis NS,Stamou D

更新日期：2015-03-01 00:00:00

abstract：:Natural enzymes have evolved to perform their cellular functions under complex selective pressures, which often require their catalytic activities to be regulated by other proteins. We contrasted a natural enzyme, LovD, which acts on a protein-bound (LovF) acyl substrate, with a laboratory-generated variant that was t...

journal_title：Nature chemical biology

authors： Jiménez-Osés G,Osuna S,Gao X,Sawaya MR,Gilson L,Collier SJ,Huisman GW,Yeates TO,Tang Y,Houk KN

更新日期：2014-06-01 00:00:00

abstract：:Using linewidth and spinning sideband intensities of lipid hydrocarbon chain resonances in proton magic angle spinning NMR spectra, we detected the temperature-dependent phase state of naturally occurring lipids of intact influenza virus without exogenous probes. Increasingly, below 41 degrees C ordered and disordered...

journal_title：Nature chemical biology

authors： Polozov IV,Bezrukov L,Gawrisch K,Zimmerberg J

更新日期：2008-04-01 00:00:00

abstract：:Although the protein synthesis inhibitor cycloheximide (CHX) has been known for decades, its precise mechanism of action remains incompletely understood. The glutarimide portion of CHX is seen in a family of structurally related natural products including migrastatin, isomigrastatin and lactimidomycin (LTM). We found ...

journal_title：Nature chemical biology

authors： Schneider-Poetsch T,Ju J,Eyler DE,Dang Y,Bhat S,Merrick WC,Green R,Shen B,Liu JO

更新日期：2010-03-01 00:00:00