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 rapidly growing field that offers potential advantages over traditional lead-discovery processes. However, identifying and assembling the fragments themselves can be challenging. Here, we review the concept of site-directed ligand discovery, in which a covalent bond is used to stabilize the interaction between a low-affinity fragment and a target protein. We also describe how this technique can facilitate fragment-based lead discovery and help overcome some of the limitations of traditional screening methods.
journal_name
Curr Opin Chem Bioljournal_title
Current opinion in chemical biologyauthors
Erlanson DA,Hansen SKdoi
10.1016/j.cbpa.2004.06.010subject
Has Abstractpub_date
2004-08-01 00:00:00pages
399-406issue
4eissn
1367-5931issn
1879-0402pii
S1367593104000869journal_volume
8pub_type
杂志文章,评审abstract：:Developing technologies such as unnatural amino acid mutagenesis, non-natural cofactor engineering, and computational design are generating proteins with novel functions; these proteins, however, often do not reach performance targets and would benefit from further optimization. Evolutionary methods can complement the...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2010.11.020
更新日期：2011-04-01 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 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：:Metabolomics and lipidomics aim to comprehensively measure the dynamic changes of all metabolites and lipids that are present in biological systems. The use of ion mobility-mass spectrometry (IM-MS) for metabolomics and lipidomics has facilitated the separation and the identification of metabolites and lipids in compl...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.10.033
更新日期：2018-02-01 00:00:00
abstract：:Compartmentalization is one of the defining features of life. Cells use protein compartments to exert spatial control over their metabolism, store nutrients and create unique microenvironments needed for essential physiological processes. Encapsulins are a recently discovered class of protein nanocompartments found in...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2016.05.013
更新日期：2016-10-01 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：:DNA binding and transcriptional activation by basic region leucine zipper (bZIP) proteins can be enhanced by accessory factors. In the past year, three accessory factor-bZIP-DNA complexes have been investigated extensively. Experiments have probed the effect of accessory factors on bZIP-DNA specificity, the residues t...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(98)80031-8
更新日期：1998-02-01 00:00:00
abstract：:The industrial application of enzymes that can withstand harsh conditions has greatly increased over the past decade. This is mainly a result of the discovery of novel enzymes from extremophilic microorganisms. Recent advances in the study of extremozymes point to the acceleration of this trend. In particular, enzymes...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(00)00183-6
更新日期：2001-04-01 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：: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：:The micro-environment in which stem cells reside regulates their fate, and synthetic materials have recently been designed to emulate these regulatory processes for various medical applications. Ligands inspired by the natural extracellular matrix, cell-cell contacts, and growth factors have been incorporated into syn...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2007.05.030
更新日期：2007-08-01 00:00:00
abstract：:Although new detection screening methods must still be developed, the actual main limitation in combinatorial chemistry seems to be the diversity of ligands that can be generated in terms of real structural and chemical diversity. Thus, there is a strong interest for the development of different strategies for the par...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2004.04.006
更新日期：2004-06-01 00:00:00
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 impl...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2006.06.003
更新日期：2006-08-01 00:00:00
abstract：:Study of protein adsorption to solid surfaces continues to be substantial because of its role in cellular responses to biomaterials, interest in molecular aspects such as conformation and orientation, new methods for making protein repellent surfaces, and new application areas such as nanoparticles and microfluidics. ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2011.04.016
更新日期：2011-10-01 00:00:00
abstract：:Molecular oxygen plays an indispensable role as a terminal electron acceptor in the electron transport chain in mitochondria. Acute or chronic oxygen deprivation (hypoxia) in organisms results in various diseases, and the elucidation of the pathogenic mechanism of hypoxia-related diseases and various cellular response...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2016.05.017
更新日期：2016-08-01 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：:The number of new chemical entities has remained rather constant (averaging 37 per year) in the past decade, despite the multiple-fold increase in the number of compounds that are being made and tested. Chemical space requires novel methods that can handle the increasing number of potentially accessible molecules. Nei...
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：:Biosensors use biological elements to detect or quantify an analyte of interest. In bioprocessing, biosensors are employed to monitor key metabolites. There are two main types: fully biological systems or biological recognition coupled with physical/chemical detection. New developments in chemical biosensors include m...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.05.014
更新日期：2017-10-01 00:00:00
abstract：:Electron bifurcation, or the coupling of exergonic and endergonic oxidation-reduction reactions, was discovered by Peter Mitchell and provides an elegant mechanism to rationalize and understand the logic that underpins the Q cycle of the respiratory chain. Thought to be a unique reaction of respiratory complex III for...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2018.07.026
更新日期：2018-12-01 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：:Technological advances in the automation of parallel synthesis are following the model set by the semiconductor industry: miniaturization, increasing speed, lower costs. Recent work includes preparation of high-density reaction blocks, development of ink-jet dispensing to polypropylene sheets and synthesis inside cust...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(97)80110-x
更新日期：1997-06-01 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：:Significant advances have been made over the past decade on illustrating structural and functional features underneath the selective metal ion recognition by various proteins in nature. These efforts led to fruitful information regarding mechanisms that bacteria employed on the regulation, transportation, and utilizat...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2007.12.010
更新日期：2008-04-01 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：: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：:The broad utility of protein bioconjugates has created a need for new and diverse strategies for site-selective protein modification. In particular, chemical reactions that target alternative amino acid side chains or unnatural functional groups are emerging as a valuable complement to more commonly used lysine- and c...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2006.04.009
更新日期：2006-06-01 00:00:00
abstract：:The field of computational protein design is reaching its adolescence. Protein design algorithms have been applied to design or engineer proteins that fold, fold faster, catalyze, catalyze faster, signal, and adopt preferred conformational states. Further developments of scoring functions, sampling strategies, and opt...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(01)00267-8
更新日期：2001-12-01 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：: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：:Metallodrugs are extensively used to treat and diagnose distinct disease types. The unique physical-chemical properties of metal ions offer tantalizing opportunities to tailor effective scaffolds for selectively targeting specific biomolecules. Modern experimental techniques have collected a large body of structural d...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2020.07.005
更新日期：2020-08-08 00:00:00
