Lipid nanoparticles improve activity of single-stranded siRNA and gapmer antisense oligonucleotides in animals.

abstract：:Phosphorylation-dependent protein-protein interaction has rarely been targeted in medicinal chemistry. Thymoquinone, a naturally occurring antitumor agent, disrupts prephosphorylated substrate recognition by the polo-box domain of polo-like kinase 1, a key mitotic regulator responsible for various carcinogenesis when ...

journal_title：ACS chemical biology

authors： Yin Z,Song Y,Rehse PH

更新日期：2013-02-15 00:00:00

abstract：:Kinetic parameters of protein-ligand interactions are progressively acknowledged as valuable information for rational drug discovery. However, a targeted optimization of binding kinetics is not easy to achieve, and further systematic studies are necessary to increase the understanding about molecular mechanisms involv...

journal_title：ACS chemical biology

authors： Cramer J,Krimmer SG,Fridh V,Wulsdorf T,Karlsson R,Heine A,Klebe G

更新日期：2017-01-20 00:00:00

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

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

更新日期：2012-08-17 00:00:00

abstract：:Filamentous cyanobacteria belong to the most prolific producers of structurally unique and biologically active natural products, yet the majority of biosynthetic gene clusters predicted for these multicellular collectives are currently orphan. Here, we present a systems analysis of secondary metabolite gene expression...

journal_title：ACS chemical biology

authors： Dehm D,Krumbholz J,Baunach M,Wiebach V,Hinrichs K,Guljamow A,Tabuchi T,Jenke-Kodama H,Süssmuth RD,Dittmann E

更新日期：2019-06-21 00:00:00

abstract：:GPCRs mediate intracellular signaling upon external stimuli, making them ideal drug targets. However, little is known about their activation mechanisms due to the difficulty in purification. Here, we introduce a method to purify GPCRs in nanodiscs, which incorporates GPCRs into lipid bilayers immediately after membran...

journal_title：ACS chemical biology

authors： Mitra N,Liu Y,Liu J,Serebryany E,Mooney V,DeVree BT,Sunahara RK,Yan EC

更新日期：2013-03-15 00:00:00

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

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

更新日期：2007-01-23 00:00:00

abstract：:STAT family proteins are important mediators of cell signaling and represent therapeutic targets for the treatment of human diseases. Most STAT inhibitors target the protein-protein interaction domain, the SH2 domain, but specificity for a single STAT protein is often limited. Recently, we developed catechol bisphosph...

journal_title：ACS chemical biology

authors： Gräb J,Berg A,Blechschmidt L,Klüver B,Rubner S,Fu DY,Meiler J,Gräber M,Berg T

更新日期：2019-04-19 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：:The rational design of environmentally sensitive dyes with superior properties is critical for elucidating the fundamental biological processes and understanding the biophysical behavior of cell membranes. In this study, a novel group of fluorene-based push-pull probes was developed for imaging membrane lipids. The de...

journal_title：ACS chemical biology

authors： Shaya J,Collot M,Bénailly F,Mahmoud N,Mély Y,Michel BY,Klymchenko AS,Burger A

更新日期：2017-12-15 00:00:00

abstract：:N-Acetylneuraminic acid lyase (NAL) is a Class I aldolase that catalyzes the reversible condensation of pyruvate with N-acetyl-d-mannosamine (ManNAc) to yield the sialic acid N-acetylneuraminic acid (Neu5Ac). Aldolases are finding increasing use as biocatalysts for the stereospecific synthesis of complex molecules. In...

journal_title：ACS chemical biology

authors： Daniels AD,Campeotto I,van der Kamp MW,Bolt AH,Trinh CH,Phillips SE,Pearson AR,Nelson A,Mulholland AJ,Berry A

更新日期：2014-04-18 00:00:00

abstract：:Combination therapies that enhance efficacy or permit reduced dosages to be administered have seen great success in a variety of therapeutic applications. More fundamentally, the discovery of epistatic pathway interactions not only informs pharmacologic intervention but can be used to better understand the underlying ...

journal_title：ACS chemical biology

authors： Severyn B,Liehr RA,Wolicki A,Nguyen KH,Hudak EM,Ferrer M,Caldwell JS,Hermes JD,Li J,Tudor M

更新日期：2011-12-16 00:00:00

abstract：:Human glucosylcerebrosidase 2 (GBA2) of the CAZy family GH116 is responsible for the breakdown of glycosphingolipids on the cytoplasmic face of the endoplasmic reticulum and Golgi apparatus. Genetic defects in GBA2 result in spastic paraplegia and cerebellar ataxia, while cross-talk between GBA2 and GBA1 glucosylceram...

journal_title：ACS chemical biology

authors： Charoenwattanasatien R,Pengthaisong S,Breen I,Mutoh R,Sansenya S,Hua Y,Tankrathok A,Wu L,Songsiriritthigul C,Tanaka H,Williams SJ,Davies GJ,Kurisu G,Cairns JR

更新日期：2016-07-15 00:00:00

abstract：:Pathogenic Yersinia spp. secrete the effector YopJ (YopP) into host cells to counteract cytokine production and to induce programmed cell death (apoptosis). YopJ achieves these aims by inactivating mitogen-activated protein kinase (MAPK) and nuclear factor kappaB signaling pathways. YopJ was shown to bind to members o...

journal_title：ACS chemical biology

authors： Bliska JB

更新日期：2006-07-21 00:00:00

abstract：:The ubiquity of microorganisms is unparalleled in any other known organism. These creatures surround our outsides and colonize our insides, a fact that has been known for centuries. However, despite their prevalence and long study, many of their characteristics still remain largely unexplained, including how proteins ...

journal_title：ACS chemical biology

authors： Brownlee C

更新日期：2010-07-16 00:00:00

abstract：:Seasonal and pandemic influenza viruses continue to be a leading global health concern. Emerging resistance to the current drugs and the variable efficacy of vaccines underscore the need for developing new flu drugs that will be broadly effective against wild-type and drug-resistant influenza strains. Here, we report ...

journal_title：ACS chemical biology

authors： Bauman JD,Patel D,Baker SF,Vijayan RS,Xiang A,Parhi AK,Martínez-Sobrido L,LaVoie EJ,Das K,Arnold E

更新日期：2013-11-15 00:00:00

abstract：:Endothelial progenitor cells (EPCs) and endothelial cells (ECs) play a vital role in endothelialization and vascularization for tissue regeneration. Various EPC/EC targeting biomolecules have been investigated to improve tissue regeneration with limited success often due to their limited functional specificity and str...

journal_title：ACS chemical biology

authors： Hao D,Xiao W,Liu R,Kumar P,Li Y,Zhou P,Guo F,Farmer DL,Lam KS,Wang F,Wang A

更新日期：2017-04-21 00:00:00

abstract：:Invertebrate animal models (mainly the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster) are gaining momentum as screening tools in drug discovery. These organisms combine genetic amenability, low cost, and culture conditions compatible with large-scale screens. Their main advantage is to allo...

journal_title：ACS chemical biology

authors： Ségalat L

更新日期：2007-04-24 00:00:00

abstract：:We recently reported two novel tools for precisely controlling and quantifying Cas9 activity: a chemically inducible Cas9 variant (ciCas9) that can be rapidly activated by small molecules and a ddPCR assay for time-resolved measurement of DNA double strand breaks (DSB-ddPCR). Here, we further demonstrate the potential...

journal_title：ACS chemical biology

authors： Rose JC,Stephany JJ,Wei CT,Fowler DM,Maly DJ

更新日期：2018-02-16 00:00:00

abstract：:Integrins play myriad and vital roles in development and disease. They connect a cell with its surroundings and transmit chemical and mechanical signals across the plasma membrane to the cell's interior. Dissecting their roles in cell behavior is complicated by their overlapping ligand specificity and shared downstrea...

journal_title：ACS chemical biology

authors： Klim JR,Fowler AJ,Courtney AH,Wrighton PJ,Sheridan RT,Wong ML,Kiessling LL

更新日期：2012-03-16 00:00:00

abstract：:A two-way colorimetric biosensor based on unmodified gold nanoparticles (GNPs) and a switchable double-stranded DNA (dsDNA) concatemer have been demonstrated. Two hairpin probes (H1 and H2) were first designed that provided the fuels to assemble the dsDNA concatemers via hybridization chain reaction (HCR). A functiona...

journal_title：ACS chemical biology

authors： Zhu L,Shao X,Luo Y,Huang K,Xu W

更新日期：2017-05-19 00:00:00

abstract：:Base deamination is a common type of DNA damage that occurs in all organisms. DNA repair mechanisms are critical to maintain genome integrity, in which the base excision repair pathway plays an essential role. In the BER pathway, the uracil DNA glycosylase superfamily is responsible for removing the deaminated bases f...

journal_title：ACS chemical biology

authors： Zhang Z,Shen J,Yang Y,Li J,Cao W,Xie W

更新日期：2016-06-17 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：:Despite the stereospecificity of translation for l-amino acids (l-AAs) in vivo, synthetic biologists have enabled ribosomal incorporation of d-AAs in vitro toward encoding polypeptides with pharmacologically desirable properties. However, the steps in translation limiting d-AA incorporation need clarification. In this...

journal_title：ACS chemical biology

authors： Liljeruhm J,Wang J,Kwiatkowski M,Sabari S,Forster AC

更新日期：2019-02-15 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：: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 Morita-Baylis-Hillman reaction forms a carbon-carbon bond between the α-carbon of a conjugated carbonyl compound and a carbon electrophile. The reaction mechanism involves Michael addition of a nucleophile catalyst at the carbonyl β-carbon, followed by bond formation with the electrophile and catalyst disassociati...

journal_title：ACS chemical biology

authors： Bjelic S,Nivón LG,Çelebi-Ölçüm N,Kiss G,Rosewall CF,Lovick HM,Ingalls EL,Gallaher JL,Seetharaman J,Lew S,Montelione GT,Hunt JF,Michael FE,Houk KN,Baker D

更新日期：2013-04-19 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

abstract：:In urodele amphibians, an early step in limb regeneration is skeletal muscle fiber dedifferentiation into a cellulate that proliferates to contribute new limb tissue. However, mammalian muscle cannot dedifferentiate after injury. We have developed a novel, small-molecule-based method to induce dedifferentiation in mam...

journal_title：ACS chemical biology

authors： Kim WH,Jung DW,Kim J,Im SH,Hwang SY,Williams DR

更新日期：2012-04-20 00:00:00

abstract：:The heat shock response is an evolutionarily conserved, stress-responsive signaling pathway that adapts cellular proteostasis in response to pathologic insult. In metazoans, the heat shock response primarily functions through the posttranslational activation of heat shock factor 1 (HSF1), a stress-responsive transcrip...

journal_title：ACS chemical biology

authors： Ryno LM,Genereux JC,Naito T,Morimoto RI,Powers ET,Shoulders MD,Wiseman RL

更新日期：2014-06-20 00:00:00

abstract：:Allosteric inhibitors can be more difficult to optimize without an understanding of how their binding influences the conformational motions of the target. Here, we used an integrated computational and experimental approach to probe the molecular mechanism of an allosteric inhibitor of heat shock protein 70 (Hsp70). Th...

journal_title：ACS chemical biology

authors： Rinaldi S,Assimon VA,Young ZT,Morra G,Shao H,Taylor IR,Gestwicki JE,Colombo G

更新日期：2018-11-16 00:00:00