Abstract:
:We describe Scaffold Hunter, a highly interactive computer-based tool for navigation in chemical space that fosters intuitive recognition of complex structural relationships associated with bioactivity. The program reads compound structures and bioactivity data, generates compound scaffolds, correlates them in a hierarchical tree-like arrangement, and annotates them with bioactivity. Brachiation along tree branches from structurally complex to simple scaffolds allows identification of new ligand types. We provide proof of concept for pyruvate kinase.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Wetzel S,Klein K,Renner S,Rauh D,Oprea TI,Mutzel P,Waldmann Hdoi
10.1038/nchembio.187subject
Has Abstractpub_date
2009-08-01 00:00:00pages
581-3issue
8eissn
1552-4450issn
1552-4469pii
nchembio.187journal_volume
5pub_type
杂志文章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...
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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
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abstract::Polyglutamine (polyQ) stretches exceeding a threshold length confer a toxic function to proteins that contain them and cause at least nine neurological disorders. The basis for this toxicity threshold is unclear. Although polyQ expansions render proteins prone to aggregate into inclusion bodies, this may be a neuronal...
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journal_title:Nature chemical biology
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doi:10.1038/nchembio.1584
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abstract::The broad study of histone deacetylases in chemistry, biology and medicine relies on tool compounds to derive mechanistic insights. A phylogenetic analysis of class I and II histone deacetylases (HDACs) as targets of a comprehensive, structurally diverse panel of inhibitors revealed unexpected isoform selectivity even...
journal_title:Nature chemical biology
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abstract::Jasmonates are lipid-derived plant hormones that regulate plant defenses and numerous developmental processes. Although the biosynthesis and molecular function of the most active form of the hormone, (+)-7-iso-jasmonoyl-L-isoleucine (JA-Ile), have been unraveled, it remains poorly understood how the diversity of bioac...
journal_title:Nature chemical biology
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abstract::Phosphorylation and glycosylation of the tau protein, which is implicated in neurodegenerative diseases, are intimately linked. In vivo pharmacological inhibition of tau deglycosylation may be a new way to suppress abnormal tau phosphorylation, known to be involved in the formation of neurofibrillary tangles in the br...
journal_title:Nature chemical biology
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abstract::Small-molecule inhibitors of kinesin-5 (refs. 1-3), a protein essential for eukaryotic cell division, represent alternatives to antimitotic agents that target tubulin. While tubulin is needed for multiple intracellular processes, the known functions of kinesin-5 are limited to dividing cells, making it likely that kin...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio812
更新日期:2006-09-01 00:00:00
abstract::Guanine-rich DNA sequences that can adopt non-Watson-Crick structures in vitro are prevalent in the human genome. Whether such structures normally exist in mammalian cells has, however, been the subject of active research for decades. Here we show that the G-quadruplex-interacting drug pyridostatin promotes growth arr...
journal_title:Nature chemical biology
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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
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abstract::The chemical scaffolds from which screening libraries are built have strong influence on the libraries' utility for screening campaigns. Here we present analysis of the scaffold composition of several types of commercially available screening collections and compare those compositions to those of drugs and drug candid...
journal_title:Nature chemical biology
pub_type: 杂志文章
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更新日期:2007-08-01 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
pub_type: 杂志文章
doi:10.1038/nchembio.1848
更新日期:2015-08-01 00:00:00
abstract::Gut microbiota is found in virtually any metazoan, from invertebrates to vertebrates. It has long been believed that gut microbiota, more specifically, the activity of the microbiome and its metabolic products, directly influence a variety of aspects in metazoan physiology. However, the exact molecular relationship am...
journal_title:Nature chemical biology
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abstract:: ...
journal_title:Nature chemical biology
pub_type: 评论,杂志文章
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更新日期:2018-06-01 00:00:00
abstract::Nontranslational functions of vertebrate aminoacyl tRNA synthetases (aaRSs), which catalyze the production of aminoacyl-tRNAs for protein synthesis, have recently been discovered. Although these new functions were thought to be 'moonlighting activities', many are as critical for cellular homeostasis as their activity ...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
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更新日期:2013-03-01 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
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doi:10.1038/nchembio.1520
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abstract::Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2251
更新日期:2017-02-01 00:00:00
abstract::Vertebrate vision is initiated by photoisomerization of the visual pigment chromophore 11-cis-retinal and is maintained by continuous regeneration of this retinoid through a series of reactions termed the retinoid cycle. However, toxic side reaction products, especially those involving reactive aldehyde groups of the ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.759
更新日期:2011-12-25 00:00:00
abstract::Nature is a diverse and rich source of bioactive pathways or novel building blocks for synthetic biology. In this Perspective, we describe the emerging research field in which metagenomes are functionally interrogated using synthetic biology. This approach substantially expands the set of identified biological activit...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/s41589-018-0100-x
更新日期:2018-08-01 00:00:00
abstract::In this study, we demonstrate the feasibility of expanding the genetic code of Escherichia coli using its own tryptophanyl-tRNA synthetase and tRNA (TrpRS-tRNATrp) pair. This was made possible by first functionally replacing this endogenous pair with an E. coli-optimized counterpart from Saccharomyces cerevisiae, and ...
journal_title:Nature chemical biology
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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
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更新日期:2014-08-01 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...
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journal_title:Nature chemical biology
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更新日期:2011-06-17 00:00:00
abstract::A required course in communication at the graduate school level may help cure the disorder of poor scientific writing. ...
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pub_type: 社论
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更新日期:2006-09-01 00:00:00
abstract::Thiazole/oxazole-modified microcins (TOMMs) encompass a recently defined class of ribosomally synthesized natural products with a diverse set of biological activities. Although TOMM biosynthesis has been investigated for over a decade, the mechanism of heterocycle formation by the synthetase enzymes remains poorly und...
journal_title:Nature chemical biology
pub_type: 杂志文章
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更新日期:2012-04-22 00:00:00
abstract::RNA G-quadruplex (G4) structures are thought to affect biological processes, including translation and pre-mRNA splicing, but it is not possible at present to demonstrate that they form naturally at specific sequences in long functional RNA molecules. We developed a new strategy, footprinting of long 7-deazaguanine-su...
journal_title:Nature chemical biology
pub_type: 杂志文章
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更新日期:2017-01-01 00:00:00
abstract::Single-molecule observations reveal that lipid- and protein-based interactions jointly contribute to the interactions among glycosylphosphatidylinositol-anchored proteins in membranes. Understanding these interactions will help to refine long-evolving (and still debated) models of 'raft' domains in biological membrane...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1045
更新日期:2012-09-01 00:00:00
abstract::The plant hormone auxin regulates virtually every aspect of plant growth and development. Auxin acts by binding the F-box protein transport inhibitor response 1 (TIR1) and promotes the degradation of the AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) transcriptional repressors. Here we show that efficient auxin binding requires...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.926
更新日期:2012-04-01 00:00:00
abstract::DNA polymerases catalyze efficient and high-fidelity DNA synthesis. While this reaction favors nucleotide incorporation, polymerases also catalyze a reverse reaction, pyrophosphorolysis, that removes the DNA primer terminus and generates deoxynucleoside triphosphates. Because pyrophosphorolysis can influence polymeras...
journal_title:Nature chemical biology
pub_type: 杂志文章
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更新日期:2017-10-01 00:00:00
abstract::Beyond established roles in collagen biosynthesis, hypoxic signaling and fatty acid metabolism, recent reports have now revealed roles for human 2-oxoglutarate-dependent oxygenases in histone and nucleic acid demethylation and in signaling protein hydroxylation. The emerging role of these oxygenases in enabling a mult...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio0308-152
更新日期:2008-03-01 00:00:00