Abstract：
:Efficient library design is an ongoing challenge for investigators seeking novel ligands for proteins, whether for drug discovery or chemical biology. Strategies that add neglected chemistry or exclude unproductive compounds are two dominant recent themes, as is a growing awareness of molecular complexity and its implications. The choice of how complex molecules in screening libraries should be often amounts to how big they should be. Small, simple molecules have lower affinities and must be screened at high concentration, but they will also have higher hit rates. Larger compounds, on the other hand, will often more closely resemble final drugs, but because they are more highly functionalized and specific, they will have much lower hit rates. The best general-purpose screening libraries may well be those of intermediate complexity that are free of artifact-causing nuisance compounds.
journal_name
Curr Opin Chem Bioljournal_title
Current opinion in chemical biologyauthors
Irwin JJdoi
10.1016/j.cbpa.2006.06.003subject
Has Abstractpub_date
2006-08-01 00:00:00pages
352-6issue
4eissn
1367-5931issn
1879-0402pii
S1367-5931(06)00080-9journal_volume
10pub_type
杂志文章,评审abstract：:Modular peptide synthetases, which act as the protein templates for the synthesis of a large number of peptide antibiotics and siderophores, hold great potential for the development of novel compounds. Recently, significant progress has been made towards understanding their molecular architecture and substrate specifi...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(97)80051-8
更新日期：1997-12-01 00:00:00
abstract：:The biochemical activities involved in signal transduction in cells are under tight spatiotemporal regulation. To study the effects of the spatial patterning and temporal dynamics of biochemical activities on downstream signaling, researchers require methods to manipulate signaling pathways acutely and rapidly. In thi...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2016.08.012
更新日期：2016-10-01 00:00:00
abstract：:Histone proteins and their accompanying post-translational modifications have received much attention for their ability to affect chromatin structure and, hence, regulate gene expression. Recently, mass spectrometry has become an important complementary tool for the analysis of histone variants and modification sites,...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2006.11.022
更新日期：2007-02-01 00:00:00
abstract：:Inspired by advances in the ability to construct programmable circuits in living organisms, in vitro circuits are emerging as a viable platform for designing, understanding, and exploiting dynamic biochemical circuitry. In vitro systems allow researchers to directly access and manipulate biomolecular parts without the...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2012.05.179
更新日期：2012-08-01 00:00:00
abstract：:The catalytic pathways of soluble methane monooxygenase (sMMO) and cytochrome P450CAM, iron-containing enzymes, are described and compared. Recent extensive density functional ab initio electronic structure calculations have revealed many similarities in a number of the key catalytic steps, as well as some important d...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(02)00310-1
更新日期：2002-04-01 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：:Exacerbation of climate change and air pollution around the world have emphasized the necessity of replacing fossil fuels with clean and sustainable energy. Metabolic engineering has provided strategies to engineer diverse organisms for the production of biofuels from renewable carbon sources. Although some of the pro...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2020.02.009
更新日期：2020-12-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2018.09.017
更新日期：2019-04-01 00:00:00
abstract：:Major advances have been made in our understanding of cytochrome c oxidase owing to continued crystallographic work on important intermediates. This, together with a wealth of data derived from selective mutations and sophisticated spectroscopic probes, has provided significant new insights into oxidase dioxygen chemi...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(99)80024-6
更新日期：1999-04-01 00:00:00
abstract：:The global nitrogen cycle is the process in which different forms of environmental N are interconverted by microorganisms either for assimilation into biomass or in respiratory energy-generating pathways. This short review highlights developments over the last 5 years in our understanding of functionality of nitrogena...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2016.02.009
更新日期：2016-04-01 00:00:00
abstract：:Monitoring the conformational dynamics of proteins is crucial for a better understanding of their biological functions. To observe the structural dynamics of proteins, it is often necessary to study each molecule individually. To this end, single-molecule techniques have been developed such as Förster resonance energy...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2019.05.003
更新日期：2019-08-01 00:00:00
abstract：:The photorespiratory pathway, in short photorespiration, is an essential metabolite repair pathway that allows the photosynthetic CO2 fixation of plants to occur in the presence of oxygen. It is necessary because oxygen is a competing substrate of the CO2-fixing enzyme ribulose 1,5-bisphosphate carboxylase, forming 2-...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2016.09.014
更新日期：2016-12-01 00:00:00
abstract：:Natural sources offer a wealth of chemically diverse compounds that have been evolutionary preselected to modulate biochemical pathways. Several industrial and academic groups are accessing this source using advanced technology platforms. Methods have been reported to generate large and diverse natural-product librari...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(02)00338-1
更新日期：2002-08-01 00:00:00
abstract：:Small molecule production in microbial hosts is limited by the accumulation of the product inside the cell. Efflux transporters show promise as a solution to removal of the often-toxic products. Recent advances in transporter identification through expression profiling, heterologous expression, and knockout studies ha...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2015.05.019
更新日期：2015-10-01 00:00:00
abstract：:The application of molecular cloning has revealed the phenomenal diversity and complexity of the phosphodiesterase isoenzyme family. Thus, more than 30 human phosphodiesterases are now known; all are apparently necessary for the seemingly simple task of hydrolysing the 3'-ester bond of either cyclic adenosine monophos...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(98)80123-3
更新日期：1998-08-01 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
abstract：:The metal-free hydrogenase from methanogenic archaea (Hmd) is a unique enzyme: it catalyzes the reaction of its substrate, methenyl-tetrahydromethanopterin, with molecular hydrogen without the aid of a transition metal. In other words, Hmd is currently the only example of a purely organic hydrogenation catalyst. Recen...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(00)00245-3
更新日期：2001-10-01 00:00:00
abstract：:Enzymes are nature's powerful catalytic proteins to perform reactions with often outstanding activity, selectivity and specificity. Moreover, the access to non-natural functions of biocatalysts can be facilitated by enzyme engineering. While rational approaches are often focused on an enzyme's active site, from random...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2018.09.010
更新日期：2018-12-01 00:00:00
abstract：:Conceptual and computational advances triggered an explosion of designed protein structures in the recent years. Various protein fold geometries have been robustly designed with atomic accuracy, including protein folds unseen in nature. The same principles and tools have been extended to design multi-chain assemblies....
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.06.020
更新日期：2017-10-01 00:00:00
abstract：:Thrombin is a multifunctional serine protease that plays a primary role in the pathogenic pathway of thrombosis as a consequence of its actions on the two principal components of blood clots, fibrin and activated platelets. Deficiencies in available therapies, heparin and coumadin, have recently led to an intense effo...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(97)80016-6
更新日期：1997-08-01 00:00:00
abstract：:Over the past two decades, there has been intense interest in designing and implementing selective (bioorthogonal) reactions for biomolecule tracking. Here we review the most widely used bioorthogonal chemistries in live cells and animals, drawing particular attention to the unique functional groups underlying these t...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2014.07.002
更新日期：2014-08-01 00:00:00
abstract：:Given the correlation between many human diseases and mis-regulated transcription, there is a growing need for molecules that can inhibit or mimic key interactions between transcriptional activators and their binding partners. Because transcriptional activators typically participate in many different protein-protein b...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2005.08.012
更新日期：2005-10-01 00:00:00
abstract：:Transition-metal catalysis has unlocked new paradigms for the late-stage modification and cyclization of peptides by harnessing the innate reactivity of proteinogenic amino acids. The field is rapidly evolving, with recent advances encompassing three fundamental areas-heteroatom couplings, decarboxylative cross-coupli...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2018.03.019
更新日期：2018-10-01 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
abstract：:The (re)design of enzymes to catalyze 'new' reactions is a topic of considerable practical and intellectual interest. Directed evolution (random mutagenesis followed by screening/selection) has been used widely to identify novel biocatalysts. However, 'rational' approaches using either natural divergent evolution or c...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2009.01.014
更新日期：2009-02-01 00:00:00
abstract：:Recent uses of phage-displayed combinatorial peptide and cDNA libraries have proven invaluable in mapping protein-protein interactions, protein-drug interactions, and the generation of 'molecular therapeutics'. This article reviews some of the findings of the past year and points out some of the pros and cons of phage...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(01)00287-3
更新日期：2002-02-01 00:00:00
abstract：:Protein citrullination is a post-translational modification of arginine that is catalyzed by the Protein Arginine Deiminase (PAD) family of enzymes. Aberrantly increased citrullination is associated with a host of inflammatory diseases and cancer and PAD inhibitors have shown remarkable efficacy in a range of diseases...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2015.10.014
更新日期：2016-02-01 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：: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
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2015.10.012
更新日期：2016-02-01 00:00:00
abstract：:Fluorescence and reflectance spectroscopy provide the ability to assess tissue structure and metabolism in vivo in real time, providing improved diagnosis of pre-cancerous lesions. Reflectance spectroscopy can probe changes in epithelial nuclei that are important in pre-cancer detection, such as mean nuclear diameter,...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(02)00381-2
更新日期：2002-10-01 00:00:00
