Abstract：
:Combinatorial chemistry methods and high-throughput screening for leads in industrial drug discovery have generated a potential bottleneck in the optimisation processes that seek to align potency with good pharmacokinetics in order to produce good medicines. This has resulted in the need for higher throughput methods of screening for absorption, distribution, metabolism and excretion properties. Significant progress has been made in throughput of in vivo pharmacokinetic studies, with the introduction of cassette, or multiple-in-one, protocols. In this technique, typically up to ten compounds are administered in one dose and analysed concomitantly on the mass spectrometer. High-throughput methods in in vitro absorption, distribution, metabolism and excretion are less well-developed as yet, and current approaches comprise automation of well-established methods for absorption using cell lines and metabolism using liver microsomes.
journal_name
Curr Opin Chem Bioljournal_title
Current opinion in chemical biologyauthors
Tarbit MH,Berman Jdoi
10.1016/s1367-5931(98)80017-3subject
Has Abstractpub_date
1998-06-01 00:00:00pages
411-6issue
3eissn
1367-5931issn
1879-0402pii
S1367-5931(98)80017-3journal_volume
2pub_type
杂志文章abstract：:Inflammatory and autoimmune diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, psoriasis and asthma, provide drug discoverers with a tremendous challenge. The precise causes of these diseases are not known, but our understanding of the molecular and cellular mechanisms associate...
journal_title：Current opinion in chemical biology
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doi：10.1016/S1367-5931(99)80071-4
更新日期：1999-08-01 00:00:00
abstract：:Simple surfactants achieve remarkable long-range order in aqueous environments. This organizing potential is seen most dramatically in biological membranes where phospholipid assemblies both define cell boundaries and provide a ubiquitous structural scaffold for controlling cellular chemistry. Here we consider simple ...
journal_title：Current opinion in chemical biology
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abstract：:The first photocaged complexes appeared in the mid-1980s specifically to complement the ongoing work studying intracellular Ca(2+) signaling with fluorescent probes. Recently, the field of biological inorganic chemistry has focused increasingly on the homeostasis mechanisms and possible signaling functions of transiti...
journal_title：Current opinion in chemical biology
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abstract：:Polyketides are a large class of structurally diverse, biologically active natural products. Recent experiments add evidence that many of the enzymes involved in the biosynthesis of these natural products are intrinsically tolerant of nonnatural substrates. In addition, an increasing understanding of structure-functio...
journal_title：Current opinion in chemical biology
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更新日期：2002-12-01 00:00:00
abstract：:Mass spectrometry has become a choice method for broad-spectrum metabolite analysis in both fundamental and applied research. This can range from comprehensive analysis achieved through time-consuming chromatography to the rapid analysis of a few target metabolites without chromatography. In this review article, we hi...
journal_title：Current opinion in chemical biology
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doi：10.1016/j.cbpa.2015.10.012
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abstract：:To date, the vast majority of the proteomic data sets collected by mass spectrometry (MS) have been generated by nondirected methods, whereby the identified precursor ions are stochastically selected for sequencing from complex sample mixtures. Recently, new MS approaches have been developed in which the mass spectrom...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
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更新日期：2009-12-01 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：:There is currently intense interest in unravelling the modus operandi of type I modular polyketide synthases in order to lay the ground work for their use in the combinatorial biosynthesis of new bioactive molecules. Much of our knowledge is derived from studies on 6-deoxyerythronolide B (DEBS), the enzyme assembling ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
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更新日期：1999-10-01 00:00:00
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journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
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journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(02)00329-0
更新日期：2002-06-01 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
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更新日期：1997-10-01 00:00:00
abstract：:Cellular communication drives diverse aspects of organismal biology ranging from immune function to memory formation. The mechanisms by which cells transact information in vivo, though, are not completely understood. This is due, in part, to a lack of tools for observing collections of cells in their native habitats. ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2014.11.006
更新日期：2015-02-01 00:00:00
abstract：:This review explores the concept of using privileged scaffolds to identify biologically active compounds through building chemical libraries. We hope to accomplish three main objectives: to provide one of the most comprehensive listings of privileged scaffolds; to reveal through four selected examples the present stat...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2010.02.018
更新日期：2010-06-01 00:00:00
abstract：:Metabolic oligosaccharide engineering and chemoenzymatic glycan labeling have provided powerful tools to study glycans in living systems and tissue samples. In this review article, we summarize recent advances in this field with a focus on innovative approaches for glycan imaging. The presented applications demonstrat...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.04.018
更新日期：2017-08-01 00:00:00
abstract：:Bacterial-derived antimicrobial polypeptides enjoy a large degree of structural and chemical diversity. Two well-studied examples of such polypeptides are the lanthionine-containing lantibiotics produced by a variety of Gram-positive bacteria, and their Gram-negative counterparts, the microcins. Both groups are produc...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(00)00094-6
更新日期：2000-06-01 00:00:00
abstract：:Initiating and terminating free-radical reactionis via hydrogen atom transfer (HAT) is an attractive means of avoiding substrate prefunctionalization. Small molecule catalysts and reagents, however, struggle to execute this fundamental step with useful levels of diastereoselectivity and enantioselectivity. In contrast...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2018.09.001
更新日期：2019-04-01 00:00:00
abstract：:The definition of molecular diversity and the development of measures for assessing the similarity or dissimilarity of molecules are central tasks for the design of novel biologically active compounds. Combinatorial chemistry allows the coupling of mathematical optimisation methods that do not require the a priori kno...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(98)80013-6
更新日期：1998-06-01 00:00:00
abstract：:Lipopolysaccharide (LPS), a glycolipid found in the outer membrane of Gram-negative bacteria, is a potent elicitor of innate immune responses in mammals. A typical LPS molecule is composed of three different structural domains: a polysaccharide called the O-antigen, a core oligosaccharide, and Lipid A. Lipid A is the ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.07.008
更新日期：2017-10-01 00:00:00
abstract：:Nitrogenase catalyzes the important reactions of N2-reduction, CO-reduction and CO2-reduction at its active cofactor site. Designated the M-cluster, this complex metallocofactor is assembled through the generation of a characteristic 8Fe-core before the insertion of Mo and homocitrate that completes the stoichiometry ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2016.02.016
更新日期：2016-04-01 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
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更新日期：2017-04-01 00:00:00
abstract：:To improve the deconstruction of biomass, the most abundant terrestrial source of carbon polymers, en route to renewable fuels, chemicals, and materials more knowledge is needed into the mechanistic interplay between thermochemical pretreatment and enzymatic hydrolysis. In this review we highlight recent progress in a...
journal_title：Current opinion in chemical biology
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更新日期：2015-12-01 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：:The design of dimeric coiled-coils has ultimately led to novel applications, such as self-replicating peptide systems, whereas the structural features of the less common trimeric coiled-coil continue to be elucidated. Novel topologies have been discovered in designed proteins, as exemplified by the right-handed tetram...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(99)00031-9
更新日期：1999-12-01 00:00:00
abstract：:Four-electron reduction of dioxygen to water and splitting of water to dioxygen are extremely important processes in the context of attaining clean renewable energy sources. High-valent metal-oxo cores are proposed as reactive intermediates in these vital processes, although they have only been isolated in extremely r...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2015.01.014
更新日期：2015-04-01 00:00:00
abstract：:A broad range of biochemicals, from proteins to nucleic acids, function properly only when associated with a metal, usually a divalent cation. Not any divalent metal will do: these metals differ in their ionic radius, dissociation in water, ionization potential, and number of unpaired electrons in their outer shells, ...
journal_title：Current opinion in chemical biology
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doi：10.1016/j.cbpa.2018.09.017
更新日期：2019-04-01 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：:Protein-polymer conjugates are of interest to researchers in diverse fields. Attachment of polymers to proteins results in improved pharmacokinetics, which is important in medicine. From an engineering standpoint, conjugates are exciting because they exhibit properties of both the biomolecules and synthetic polymers. ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2010.10.008
更新日期：2010-12-01 00:00:00
abstract：:Nucleic acids such as DNA are increasingly being applied in nanotechnology, as a result of their capability to self-assemble reversibly. The formal replacement of canonical base pairs by metal-mediated ones enables a site-specific introduction of metal-based functionality into these biomolecules, leading to the format...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.01.019
更新日期：2017-04-01 00:00:00
abstract：:A number of nitrile-related enzymes have been screened over the past year for use in synthetic applications. There have also been significant advances in our understanding of the structures and modes of regulation of metal-containing nitrile hydratases. Enzyme structural characterization has provided new insights into...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(99)00058-7
更新日期：2000-02-01 00:00:00
abstract：:The cytochrome bc(1) complex is a key mitochondrial enzyme that catalyses transfer of electrons maintaining the membrane potential of mitochondria. Currently, atovaquone is the only drug in clinical use targeting the Plasmodium falciparum bc(1) complex. The rapid emergence of resistance to atovaquone resulted in a cos...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2010.05.005
更新日期：2010-08-01 00:00:00
