Abstract：
:The past decade has seen rapid growth in the use of diverse compound libraries in classical phenotypic screens to identify modulators of a given process. The subsequent process of identifying the molecular targets of active hits, also called 'target deconvolution', is an essential step for understanding compound mechanism of action and for using the identified hits as tools for further dissection of a given biological process. Recent advances in 'omics' technologies, coupled with in silico approaches and the reduced cost of whole genome sequencing, have greatly improved the workflow of target deconvolution and have contributed to a renaissance of 'modern' phenotypic profiling. In this review, we will outline how both new and old techniques are being used in the difficult process of target identification and validation as well as discuss some of the ongoing challenges remaining for phenotypic screening.
journal_name
Curr Opin Chem Bioljournal_title
Current opinion in chemical biologyauthors
Lee J,Bogyo Mdoi
10.1016/j.cbpa.2012.12.022subject
Has Abstractpub_date
2013-02-01 00:00:00pages
118-26issue
1eissn
1367-5931issn
1879-0402pii
S1367-5931(13)00002-1journal_volume
17pub_type
杂志文章,评审abstract：:Significant progress in our understanding of the mechanism of fatty acid desaturation has been achieved. The site of initial oxidation has been determined for several membrane-bound desaturases and a common cryptoregiochemical theme has been revealed. The results of several studies, including a detailed analysis of a ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(02)00365-4
更新日期：2002-10-01 00:00:00
abstract：:A variety of protein sequence databases exist, ranging from simple sequence repositories, which store data with little or no manual intervention in the creation of the records, to expertly curated universal databases that cover all species and in which the original sequence data are enhanced by the manual addition of ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2003.12.004
更新日期：2004-02-01 00:00:00
abstract：:Majority of eukaryotic proteins are glycosylated and their glycan moieties have numerous important structural, functional and regulatory roles. Because of structural complexity of glycans and technological limitations glycomics, and particularly glycoproteomics was not able to follow rapid progress in genomics and pro...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2012.12.007
更新日期：2013-02-01 00:00:00
abstract：:Rapid progress in genomics and proteomics has provided a wealth of new targets for the pharmaceutical industry, even as many older targets still remain challenging for small-molecule drug discovery. Fragment-based lead discovery, in which leads are built progressively by expanding or combining small fragments, is a ra...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2004.06.010
更新日期：2004-08-01 00:00:00
abstract：:Allosteric binding sites, as opposed to traditional orthosteric binding sites, offer unparalleled opportunities for drug discovery by providing high levels of selectivity, mimicking physiological conditions, affording fewer side effects because of desensitization/downregulation, and engendering ligands with chemotypes...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2008.02.014
更新日期：2008-06-01 00:00:00
abstract：:Chemical manipulation of natural, unengineered proteins is a daunting challenge which tests the limits of reaction design. By combining transition-metal or other catalysts with molecular recognition ideas, it is possible to achieve site-selective protein reactivity without the need for engineered recognition sequences...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2014.12.017
更新日期：2015-04-01 00:00:00
abstract：:Single nucleotide polymorphism (SNP) genotyping has become a key technology for genetic studies. In recent years, matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry has emerged as a very powerful method for SNP genotyping. Here, we discuss our experience in implementing a high-through...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(01)00290-3
更新日期：2002-02-01 00:00:00
abstract：:Due to the existence of numerous isomers, the in-depth analysis of glycans represents a major challenge. Currently, the majority of glycans are analysed using mass spectrometry (MS)-based techniques, which can provide information on regioisomers but usually fail to differentiate stereoisomers. A promising approach to ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.10.021
更新日期：2018-02-01 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：:Within this review article we describe recent developments in asymmetric catalysis with peptides. Numerous peptides have been established in the past two decades that catalyze a wide variety of transformations with high stereoselectivities and yields, as well as broad substrate scope. We highlight here catalytically a...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2014.09.011
更新日期：2014-10-01 00:00:00
abstract：:Medicinal chemistry principles are being increasingly applied to the design of smaller, high purity, information-rich libraries. Recent computational advances in statistical methodology, the design of libraries to reduce ADMET problems, targeting protein families and revisiting natural products as sources of inspirati...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(03)00057-7
更新日期：2003-06-01 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：: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：:Recent advances in -omic profiling technologies have ushered in an era where we no longer want to merely measure the presence or absence of a biomolecule of interest, but instead hope to understand its function and interactions within larger signaling networks. Here, we review several emerging proteomic technologies c...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2020.02.001
更新日期：2020-02-01 00:00:00
abstract：:The fermentation of synthesis gas (including carbon monoxide, carbon dioxide, and hydrogen) with anaerobic acetogens is an established biotechnological process that has recently been transferred to a commercial scale. The natural product spectrum of acetogens is natively restricted to acetate, ethanol, and 2,3-butaned...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.10.003
更新日期：2017-12-01 00:00:00
abstract：:Synthetic biologists typically construct new pathways within existing cells. While useful, this approach in many ways ignores the undefined but necessary components of life. A growing number of laboratories have begun to try to remove some of the mysteries of cellular life by building life-like systems from non-living...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2012.10.020
更新日期：2012-12-01 00:00:00
abstract：:Systems modeling is emerging as a valuable tool in therapeutics. This is seen by the increasing use of clinically relevant computational models and a rise in systems biology companies working with the pharmaceutical industry. Systems models have helped understand the effects of pharmacological intervention at receptor...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2005.06.008
更新日期：2005-08-01 00:00:00
abstract：:Extracellular electron transfer via filamentous protein appendages called 'microbial nanowires' has long been studied in Geobacter and other bacteria because of their crucial role in globally-important environmental processes and their applications for bioenergy, biofuels, and bioelectronics. Thousands of papers thoug...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2020.08.004
更新日期：2020-12-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2009.09.027
更新日期：2009-12-01 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：:Structural modification of naturally occurring beta-lactams and beta-lactones is a highly effective strategy for generating drugs for treating bacterial infections, cancer, obesity, and hyperlipidemia. These drugs acylate catalytic amino acids (serine, threonine, or cysteine) in enzyme targets such as penicillin-bindi...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2010.03.035
更新日期：2010-06-01 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：: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：:Lipids are a vital class of molecules that play important and varied roles in biological processes, however, fully understanding these roles is extremely difficult due to the immense number and diversity of possible lipid species. While recent advances in chromatography and high resolution mass spectrometry have great...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.11.009
更新日期：2018-02-01 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：: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：: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：:Numerous developments in useful linkers are closely related with the advances in solid-phase organic synthesis. These linkers allow facile attachment functionalization and release molecules of interest. Designing a new anchoring group can be essential for synthesis success, especially for small molecules on solid supp...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2004.04.004
更新日期：2004-06-01 00:00:00
abstract：:Complex glycans participate in many essential life processes. Studies of glycan-mediated biological events have traditionally employed structurally defined fragments of the more elaborate natural molecules. However, it is now clear that this approach may sometimes be insufficient and this realization has prompted a de...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2013.10.009
更新日期：2013-12-01 00:00:00
abstract：:A wide assortment of caged compounds, which are species whose biological activity can be unleashed with light, have been synthesized and used to investigate a variety of biological phenomena. In contrast, the construction of caged proteins and their application to biological systems has lagged far behind. Recent advan...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(99)80015-5
更新日期：1999-02-01 00:00:00
