Unifying principles of bifunctional, proximity-inducing small molecules.

abstract：:Cholinesterase inhibitors, the current frontline symptomatic treatment for Alzheimer's disease (AD), are associated with low efficacy and adverse effects. M1 muscarinic acetylcholine receptors (M1 mAChRs) represent a potential alternate therapeutic target; however, drug discovery programs focused on this G protein-cou...

journal_title：Nature chemical biology

authors： Bradley SJ,Molloy C,Valuskova P,Dwomoh L,Scarpa M,Rossi M,Finlayson L,Svensson KA,Chernet E,Barth VN,Gherbi K,Sykes DA,Wilson CA,Mistry R,Sexton PM,Christopoulos A,Mogg AJ,Rosethorne EM,Sakata S,John Challiss RA,B

更新日期：2020-03-01 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：:Drug discovery resources in academia and industry are not used efficiently, to the detriment of industry and society. Duplication could be reduced, and productivity could be increased, by performing basic biology and clinical proofs of concept within open access industry-academia partnerships. Chemical biologists coul...

journal_title：Nature chemical biology

authors： Edwards AM,Bountra C,Kerr DJ,Willson TM

更新日期：2009-07-01 00:00:00

abstract：:Linking bioactive compounds to their cellular targets is a central challenge in chemical biology. Here we report the mode of action of theonellamides, bicyclic peptides derived from marine sponges. We generated a chemical-genomic profile of theonellamide F using a collection of fission yeast strains in which each open...

journal_title：Nature chemical biology

authors： Nishimura S,Arita Y,Honda M,Iwamoto K,Matsuyama A,Shirai A,Kawasaki H,Kakeya H,Kobayashi T,Matsunaga S,Yoshida M

更新日期：2010-07-01 00:00:00

abstract：:Proper gene expression is essential for the survival of every cell. Once thought to be a passive transporter of genetic information, RNA has recently emerged as a key player in nearly every pathway in the cell. A full description of its structure is critical to understanding RNA function. Decades of research have focu...

journal_title：Nature chemical biology

authors： Kubota M,Tran C,Spitale RC

更新日期：2015-12-01 00:00:00

abstract：:The P1B-ATPases, which couple cation transport across membranes to ATP hydrolysis, are central to metal homeostasis in all organisms. An important feature of P1B-ATPases is the presence of soluble metal binding domains (MBDs) that regulate transport activity. Only one type of MBD has been characterized extensively, bu...

journal_title：Nature chemical biology

authors： Smith AT,Barupala D,Stemmler TL,Rosenzweig AC

更新日期：2015-09-01 00:00:00

abstract：:Twister is a small ribozyme present in almost all kingdoms of life that rapidly self-cleaves in variety of divalent metal ions. We used activity assays, bulk FRET and single-molecule FRET (smFRET) to understand how different metal ions promote folding and self-cleavage of the Oryza sativa twister ribozyme. Although mo...

journal_title：Nature chemical biology

authors： Panja S,Hua B,Zegarra D,Ha T,Woodson SA

更新日期：2017-10-01 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

abstract：:Studies of gene function and molecular mechanisms in Plasmodium falciparum are hampered by difficulties in characterizing and measuring phenotypic differences between individual parasites. We screened seven parasite lines for differences in responses to 1,279 bioactive chemicals. Hundreds of compounds were active in i...

journal_title：Nature chemical biology

authors： Yuan J,Johnson RL,Huang R,Wichterman J,Jiang H,Hayton K,Fidock DA,Wellems TE,Inglese J,Austin CP,Su XZ

更新日期：2009-10-01 00:00:00

abstract：:Hundreds of human proteins are modified by reversible palmitoylation of cysteine residues (S-palmitoylation), but the regulation of depalmitoylation is poorly understood. Here, we develop 'depalmitoylation probes' (DPPs), small-molecule fluorophores, to monitor the endogenous activity levels of 'erasers' of S-palmitoy...

journal_title：Nature chemical biology

authors： Kathayat RS,Elvira PD,Dickinson BC

更新日期：2017-02-01 00:00:00

abstract：:Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. We hypothesized that differential basal gene expression could be correlated with patterns of small-molecule sensitivity ...

journal_title：Nature chemical biology

authors： Rees MG,Seashore-Ludlow B,Cheah JH,Adams DJ,Price EV,Gill S,Javaid S,Coletti ME,Jones VL,Bodycombe NE,Soule CK,Alexander B,Li A,Montgomery P,Kotz JD,Hon CS,Munoz B,Liefeld T,Dančík V,Haber DA,Clish CB,Bittker JA

更新日期：2016-02-01 00:00:00

abstract：:It is postulated that in addition to cell density, other factors such as the dimensions and diffusional characteristics of the environment could influence quorum sensing (QS) and induction of genetic reprogramming. Modeling studies predict that QS may operate at the level of a single cell, but, owing to experimental c...

journal_title：Nature chemical biology

authors： Carnes EC,Lopez DM,Donegan NP,Cheung A,Gresham H,Timmins GS,Brinker CJ

更新日期：2010-01-01 00:00:00

abstract：:Lipid rafts in plasma membranes have emerged as possible platforms for the entry of HIV and other viruses into cells. However, little is known about how lipid phase heterogeneity contributes to viral entry because of the fine-grained and still poorly understood complexity of biological membranes. We used model systems...

journal_title：Nature chemical biology

authors： Yang ST,Kiessling V,Simmons JA,White JM,Tamm LK

更新日期：2015-06-01 00:00:00

abstract：:N6-Methyladenosine (m6A) RNA modification is present in messenger RNAs (mRNA), ribosomal RNAs (rRNA), and spliceosomal RNAs (snRNA) in humans. Although mRNA m6A modifications have been extensively studied and shown to play critical roles in many cellular processes, the identity of m6A methyltransferases for rRNAs and ...

journal_title：Nature chemical biology

authors： Ma H,Wang X,Cai J,Dai Q,Natchiar SK,Lv R,Chen K,Lu Z,Chen H,Shi YG,Lan F,Fan J,Klaholz BP,Pan T,Shi Y,He C

更新日期：2019-01-01 00:00:00

abstract：:The N-end rule pathway senses the N-terminal destabilizing residues of degradation substrates for the ubiquitin-proteasome system, whose integrity shields against various human syndromes including cancer and cardiovascular diseases. GID4, a subunit of the ubiquitin ligase GID complex, has been recently identified as t...

journal_title：Nature chemical biology

authors： Dong C,Zhang H,Li L,Tempel W,Loppnau P,Min J

更新日期：2018-05-01 00:00:00

abstract：:Subtilosin A is a 35-residue, ribosomally synthesized bacteriocin encoded by the sbo-alb operon of Bacillus subtilis. It is composed of a head-to-tail circular peptide backbone that is additionally restrained by three unusual thioether bonds between three cysteines and the α-carbon of one threonine and two phenylalani...

journal_title：Nature chemical biology

authors： Flühe L,Knappe TA,Gattner MJ,Schäfer A,Burghaus O,Linne U,Marahiel MA

更新日期：2012-02-26 00:00:00

abstract：:Bacterial biofilms can be programmed to produce living materials with self-healing and evolvable functionalities. However, the wider use of artificial biofilms has been hindered by limitations on processability and functional protein secretion capacity. We describe a highly flexible and tunable living functional mater...

journal_title：Nature chemical biology

authors： Huang J,Liu S,Zhang C,Wang X,Pu J,Ba F,Xue S,Ye H,Zhao T,Li K,Wang Y,Zhang J,Wang L,Fan C,Lu TK,Zhong C

更新日期：2019-01-01 00:00:00

abstract：:5-Formylcytosine (5fC) is a rare base found in mammalian DNA and thought to be involved in active DNA demethylation. Here, we show that developmental dynamics of 5fC levels in mouse DNA differ from those of 5-hydroxymethylcytosine (5hmC), and using stable isotope labeling in vivo, we show that 5fC can be a stable DNA ...

journal_title：Nature chemical biology

authors： Bachman M,Uribe-Lewis S,Yang X,Burgess HE,Iurlaro M,Reik W,Murrell A,Balasubramanian S

更新日期：2015-08-01 00:00:00

abstract：:Miniproteins simplify the protein-folding problem, allowing the dissection of forces that stabilize protein structures. Here we describe PPα-Tyr, a designed peptide comprising an α-helix buttressed by a polyproline II helix. PPα-Tyr is water soluble and monomeric, and it unfolds cooperatively with a midpoint unfolding...

journal_title：Nature chemical biology

authors： Baker EG,Williams C,Hudson KL,Bartlett GJ,Heal JW,Porter Goff KL,Sessions RB,Crump MP,Woolfson DN

更新日期：2017-07-01 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：:Small molecules stabilize specific protein conformations from a larger ensemble, enabling molecular switches that control diverse cellular functions. We show here that the converse also holds true: the conformational state of the estrogen receptor can direct distinct orientations of the bound ligand. 'Gain-of-alloster...

journal_title：Nature chemical biology

authors： Bruning JB,Parent AA,Gil G,Zhao M,Nowak J,Pace MC,Smith CL,Afonine PV,Adams PD,Katzenellenbogen JA,Nettles KW

更新日期：2010-11-01 00:00:00

abstract：:Drugs with prolonged on-target residence times often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here we made progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Using an ...

journal_title：Nature chemical biology

authors： Bradshaw JM,McFarland JM,Paavilainen VO,Bisconte A,Tam D,Phan VT,Romanov S,Finkle D,Shu J,Patel V,Ton T,Li X,Loughhead DG,Nunn PA,Karr DE,Gerritsen ME,Funk JO,Owens TD,Verner E,Brameld KA,Hill RJ,Goldstein DM,

更新日期：2015-07-01 00:00:00

abstract：:Proteome integrity depends on the ubiquitin-proteasome system to degrade unwanted or abnormal proteins. In addition to the N-degrons, C-terminal residues of proteins can also serve as degradation signals (C-degrons) that are recognized by specific cullin-RING ubiquitin ligases (CRLs) for proteasomal degradation. FEM1C...

journal_title：Nature chemical biology

authors： Yan X,Wang X,Li Y,Zhou M,Li Y,Song L,Mi W,Min J,Dong C

更新日期：2021-01-04 00:00:00

abstract：:We document a new dimension of surface recognition in which communication is controlled through the collective behavior of lipids. Membrane cholesterol induces a tilt in glycolipid receptor headgroup, resulting in loss of access for ligand binding. This property appears to organize erythrocyte blood group presentation...

journal_title：Nature chemical biology

authors： Lingwood D,Binnington B,Róg T,Vattulainen I,Grzybek M,Coskun U,Lingwood CA,Simons K

更新日期：2011-05-01 00:00:00

abstract：:The rise of antibiotic resistance demands the acceleration of molecular diversification strategies to inspire new chemical entities for antibiotic medicines. We report here on the large-scale engineering of ribosomally synthesized and post-translationally modified antimicrobial peptides carrying the ring-forming amino...

journal_title：Nature chemical biology

authors： Schmitt S,Montalbán-López M,Peterhoff D,Deng J,Wagner R,Held M,Kuipers OP,Panke S

更新日期：2019-05-01 00:00:00

abstract：:The chemical species involved in H2S signaling remain elusive despite the profound and pleiotropic physiological effects elicited by this molecule. The dominant candidate mechanism for sulfide signaling is persulfidation of target proteins. However, the relatively poor reactivity of H2S toward oxidized thiols, such as...

journal_title：Nature chemical biology

authors： Mishanina TV,Libiad M,Banerjee R

更新日期：2015-07-01 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：:Antibody-drug conjugates (ADCs) selectively deliver chemotherapeutic agents to target cells and are important cancer therapeutics. However, the mechanisms by which ADCs are internalized and activated remain unclear. Using CRISPR-Cas9 screens, we uncover many known and novel endolysosomal regulators as modulators of AD...

journal_title：Nature chemical biology

authors： Tsui CK,Barfield RM,Fischer CR,Morgens DW,Li A,Smith BAH,Gray MA,Bertozzi CR,Rabuka D,Bassik MC

更新日期：2019-10-01 00:00:00

abstract：:The simultaneous observation of interdependent reactions within different phases as catalyzed by membrane-bound enzymes is still a challenging task. One such enzyme, the Escherichia coli integral membrane protein diacylglycerol kinase (DGK), is a key player in lipid regulation. It catalyzes the generation of phosphati...

journal_title：Nature chemical biology

authors： Ullrich SJ,Hellmich UA,Ullrich S,Glaubitz C

更新日期：2011-05-01 00:00:00

abstract：:The eukaryotic replicative DNA polymerases (Pol α, δ and ɛ) and the major DNA mutagenesis enzyme Pol ζ contain two conserved cysteine-rich metal-binding motifs (CysA and CysB) in the C-terminal domain (CTD) of their catalytic subunits. Here we demonstrate by in vivo and in vitro approaches the presence of an essential...

journal_title：Nature chemical biology

authors： Netz DJ,Stith CM,Stümpfig M,Köpf G,Vogel D,Genau HM,Stodola JL,Lill R,Burgers PM,Pierik AJ

更新日期：2011-11-27 00:00:00