Abstract：
:Altered metabolite levels can drive epigenetic changes critical to development and disease. However, in many cases the specific protein-metabolite interactions that underlie this process remain enigmatic. In this review, we make the case that this fundamental missing information may be discovered by applying the tools of modern drug target validation to study endogenous metabolite pharmacology. We detail examples in which chemical proteomics has been applied to gain new insights into reversible and covalent metabolite signaling mechanisms, using acetyl-CoA and fumarate as case studies. Finally, we provide a brief survey of nascent chemical biology methods whose application to the study of endogenous metabolite pharmacology may further advance the field.
journal_name
Curr Opin Chem Bioljournal_title
Current opinion in chemical biologyauthors
Kulkarni RA,Montgomery DC,Meier JLdoi
10.1016/j.cbpa.2019.02.002subject
Has Abstractpub_date
2019-08-01 00:00:00pages
30-39eissn
1367-5931issn
1879-0402pii
S1367-5931(19)30002-Xjournal_volume
51pub_type
杂志文章,评审abstract：:Lysine acetylation has emerged as a key post-translational modification found at many sites throughout the cell. It plays an important role in epigenetic processes, and more generally in the regulation of protein stability and interactions. Acetyl groups are installed by lysine acetyltransferases and removed by lysine...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2018.06.015
更新日期：2018-08-01 00:00:00
abstract：:There is tremendous interest in developing and refining methods to predictably perform chemical reactions within the framework of living systems. Here we review recent advances in applying tetrazine cycloadditions to live cell and in vivo chemistry. We highlight new syntheses of the tetrazine and dienophile precursors...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2013.08.004
更新日期：2013-10-01 00:00:00
abstract：:Herein we review contemporary synthetic and protein design strategies to stabilize the alpha-helical motif in short peptides and miniature proteins. Advances in organometallic catalyst design, specifically for the olefin metathesis reaction, enable the use of hydrocarbon bridges to either crosslink side chains of spec...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2008.08.019
更新日期：2008-12-01 00:00:00
abstract：:Multicomponent reactions (MCRs) provide a powerful tool towards the one-pot synthesis of diverse and complex compounds on the one hand and small and 'drug-like' heterocycles on the other hand. No other single synthesis technology enables chemists to search such large chemical spaces as provided by MCRs. MCRs that invo...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(02)00328-9
更新日期：2002-06-01 00:00:00
abstract：:RNA plays an essential cellular role in nearly every aspect of the transmission and expression of genetic information, including regulatory roles that have significance for cellular development. Access to RNA bearing synthetic modifications has allowed biological chemists to probe deep into the inner workings of cellu...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2005.10.009
更新日期：2005-12-01 00:00:00
abstract：:Lipids are indispensable cellular building blocks, and their post-translational attachment to proteins makes them important regulators of many biological processes. Dysfunction of protein lipidation is also implicated in many pathological states, yet its systematic analysis presents significant challenges. Thanks to i...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2020.10.002
更新日期：2020-11-19 00:00:00
abstract：:Recent advances in multidimensional nuclear magnetic resonance methodology to obtain 1H, 15N and 13C resonance assignments, interproton distance and torsion angle restraints, and restraints that characterize long-range order, coupled with new methods of structure refinement and novel methods for reducing linewidths, h...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(98)80084-7
更新日期：1998-10-01 00:00:00
abstract：:The reactive oxygen and nitrogen species superoxide ion, nitric oxide, nitrogen dioxide and peroxynitrite ion all react with biological target molecules. Some of these interactions are carefully orchestrated segments of signal transduction cascades or part of the armamentarium of the immune system, others are patholog...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/S1367-5931(99)80036-2
更新日期：1999-04-01 00:00:00
abstract：:Phosphorus cycling in the biosphere has traditionally been thought to involve almost exclusively transformations of the element in its pentavalent oxidation state. Recent evidence, however, suggests that a significant fraction of environmental phosphorus may exist in a more reduced form. Most abundant of these reduced...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2016.01.010
更新日期：2016-04-01 00:00:00
abstract：:The field of enzymology has long used small-molecule mass spectrometry. However, the direct interrogation of covalent and non-covalent intermediates by large-molecule mass spectrometry of enzymes or large peptide substrates is illuminating an increasingly diverse array of chemistries used in nature. Recent advances no...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2005.08.018
更新日期：2005-10-01 00:00:00
abstract：:The atomic force microscope (AFM) allows biomolecules to be observed and manipulated under native conditions. It operates in buffer solution, produces molecular images with outstanding signal-to-noise ratio, and addresses single molecules. Progress in sample preparation and instrumentation has led to topographs that r...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2003.08.010
更新日期：2003-10-01 00:00:00
abstract：:The translation of nucleic acids into synthetic structures with expanded functional potential has been the subject of considerable research, with applications including small-molecule and polymer evolution, reaction discovery and sensing. Here, we review properties of nucleic-acid-templated synthesis in the context of...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2004.09.003
更新日期：2004-12-01 00:00:00
abstract：:Sugar nucleotide-modifying enzymes of the short-chain dehydrogenase/reductase type use transient oxidation-reduction by a tightly bound nicotinamide cofactor as a common strategy of catalysis to promote a diverse set of reactions, including decarboxylation, single- or double-site epimerization, and dehydration. Althou...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2020.09.010
更新日期：2020-11-06 00:00:00
abstract：:During 1996 and 1997, several chemical issues that arise in the early stages of preinitiation complex (PIC) formation were resolved. Kinetics experiments indicated that both TBP dimerization and DNA bending influence the rate of TBP-TATA box assembly. Affinity cleavage experiments indicated that TBP lacks the specific...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(98)80030-6
更新日期：1998-02-01 00:00:00
abstract：:Peptide nucleic acid (PNA)-encoded chemical libraries along with DNA-encoded libraries have provided a powerful new paradigm for library synthesis and ligand discovery. PNA-encoding stands out for its compatibility with standard solid phase synthesis and the technology has been used to prepare libraries of peptides, h...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2015.01.005
更新日期：2015-06-01 00:00:00
abstract：:Peptide arrays have attracted wide interest as tools for discovering biochemical interactions. Because many protein binding and enzyme activities are directed towards peptides, the preparation of arrays having hundreds to thousands of immobilized peptides offers an unprecedented opportunity for identifying interaction...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2004.08.007
更新日期：2004-10-01 00:00:00
abstract：:A long-standing goal of molecular imaging is to visualize cellular function within the context of living animals, necessitating the development of reporter genes compatible with deeply penetrant imaging modalities such as ultrasound and magnetic resonance imaging (MRI). Until recently, no reporter genes for ultrasound...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2018.02.011
更新日期：2018-08-01 00:00:00
abstract：:There is growing interest in the design of synthetic molecules that mimic the structures and functions of epitopes found on the surface of peptides and proteins. Epitope mimetics can provide valuable tools to probe complex biological processes, as well as interesting leads for drug and vaccine discovery. One applicati...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2011.02.015
更新日期：2011-06-01 00:00:00
abstract：:Natural enzymes that catalyze Diels-Alder reactions have long been sought after, yet few enzymes have been experimentally confirmed to perform this reaction. In the past five years, several stand-alone enzymes that can catalyze the Diels-Alder reaction had been identified and characterized. Among which, the crystal st...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2016.09.015
更新日期：2016-12-01 00:00:00
abstract：:Protein synthesis is inherently a dynamic process, requiring both small-scale and large-scale movements of tRNA and mRNA. It has long been suspected that these movements might be coupled to conformational changes in the ribosome, and in its RNA moieties in particular. Recently, the nature of ribosome structural dynami...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2008.08.037
更新日期：2008-12-01 00:00:00
abstract：:In recent years, ogliopeptides have enjoyed ever increasing interest in two areas: first, approaches to biomimetic enzyme-like activity; and second, as metal-free catalysts for enantioselective transformations of synthetic interest. The discovery and optimization of peptides for these purposes has often used the metho...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(03)00065-6
更新日期：2003-06-01 00:00:00
abstract：:The ability of cobalamin to coordinate different upper axial ligands gives rise to a diversity of reactivity. Traditionally, adenosylcobalamin is associated with radical-based rearrangements, and methylcobalamin with methyl cation transfers. Recently, however, a new role for adenosylcobalamin has been discovered as a ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.01.013
更新日期：2017-04-01 00:00:00
abstract：:NMR, already some 50 years old, has long been an invaluable analytical method in industry for verification of chemical synthesis and compound characterisation. The range of molecular information accessible through NMR, however, offers a far larger horizon of applications. Of these, ligand screening by NMR has emerged ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(00)00204-0
更新日期：2001-06-01 00:00:00
abstract：:Recent advances in the development of the phosphorescent Ir(III) complexes have made it possible to implement the phosphorescence modality in bioimaging applications. A variety of phosphorescent Ir(III) complexes have been synthesized and assessed in the context of in vitro and in vivo imaging, especially in subcellul...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2013.05.023
更新日期：2013-08-01 00:00:00
abstract：:Signal amplification in conventional enzyme-based biosensors is not high enough to achieve the ultrasensitive detection of biomolecules. In recent years, signal amplification has been improved by combining enzymatic reactions with redox cycling or employing multienzyme labels per detection probe. Electrochemical-chemi...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2012.03.015
更新日期：2012-08-01 00:00:00
abstract：:Elastin-like polypeptides (ELPs) are artificial polypeptides, derived from Val-Pro-Gly-Xaa-Gly (VPGXG) pentapeptide repeats found in human tropoelastin, that reversibly coacervate above a critical temperature. Genetically encodable ELPs are monodisperse, stimuli responsive, and biocompatible, properties that make them...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2006.10.010
更新日期：2006-12-01 00:00:00
abstract：:Inhibition of the steroid 5alpha-reductases shows promise in the treatment of a number of androgen-dependent disorders, such as benign prostatic hyperplasia, male pattern baldness, and acne. The design of potent and isozyme-selective inhibitors has provided biologists and clinicians with important tools for elucidatin...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(97)80017-8
更新日期：1997-08-01 00:00:00
abstract：:Recent efforts in expanding the range of biofuel and biorenewable molecules using microbial production hosts have focused on the introduction of non-native pathways in model organisms and the bio-prospecting of non-model organisms with desirable features. Current challenges lie in the assembly and coordinated expressi...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2015.06.026
更新日期：2015-10-01 00:00:00
abstract：:RNA editing in kinetoplastids involves post-transcriptional insertion and deletion of uridylates (Us) to produce mature mitochondrial mRNAs with sequences specified by trans acting small guide RNAs. In vitro studies indicate the reaction pathway involves endonucleolytic cleavage of the precursor mRNA at the editing si...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(97)80071-3
更新日期：1997-10-01 00:00:00
abstract：:Protein engineering over the past four years has made rhodopsin-based genetically encoded voltage indicators a leading candidate to achieve the task of reporting action potentials from a population of genetically targeted neurons in vivo. Rational design and large-scale screening efforts have steadily improved the dyn...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2015.05.006
更新日期：2015-08-01 00:00:00
