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 effort in several pharmaceutical companies to develop potent, selective, and preferably orally bioavailable direct thrombin inhibitors. Substantial progress has been made on potent and selective compounds and work is ongoing to improve other pharmacokinetic properties such as oral bioavailability and duration of action, properties necessary for successful clinical development.
journal_name
Curr Opin Chem Bioljournal_title
Current opinion in chemical biologyauthors
Ripka WCdoi
10.1016/s1367-5931(97)80016-6subject
Has Abstractpub_date
1997-08-01 00:00:00pages
242-53issue
2eissn
1367-5931issn
1879-0402pii
S1367-5931(97)80016-6journal_volume
1pub_type
杂志文章,评审abstract::The oceans are filled with an amazing variety of biological materials including the glues and cements of mussels, barnacles, tube worms, algae, and starfish. Recent studies on mussel adhesive are providing increasing evidence for a unique mechanism of material generation involving iron-induced protein oxidation and cr...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2009.11.009
更新日期:2010-04-01 00:00:00
abstract::Functional amino acids that play critical roles in catalysis and regulation are known to display elevated nucleophilicity and can be selectively targeted for covalent modification by reactive electrophiles. Chemical-proteomic platforms, such as activity-based protein profiling (ABPP), exploit this reactivity by utiliz...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2014.10.021
更新日期:2015-02-01 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::Recent studies of moonlighting functions and catalytic promiscuity provide insights into the structural and mechanistic bases of these phenomena. Moonlighting proteins that are highlighted include gephyrin, the Neurospora crassa tyrosyl tRNA synthetase, phosphoglucose isomerase, and cytochrome c. New insights into cat...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(03)00032-2
更新日期:2003-04-01 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::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::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::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::In many species, double-stranded RNA can specifically and effectively silence genes. This newly discovered biological phenomenon, called RNA interference (RNAi), has practical implications for functional genomics. As shown by two recent reports, RNAi provides a rapid method to test the function of genes in the nematod...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(00)00173-3
更新日期:2001-02-01 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::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
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(02)00360-5
更新日期:2002-12-01 00:00:00
abstract::Before large, specific peptides could be made, in an RNA world our ancestors may have used an RNA-like molecule for both catalysis and information storage. Taken together, RNA activities suggest RNA could have performed most of the essential informational functions of an ancient organism (i.e. those functions most sim...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/S1367-5931(99)80041-6
更新日期:1999-06-01 00:00:00
abstract::Genetically Encoded Voltage Indicators (GEVIs) are powerful tools used to investigate neural activity in the brain. The spatiotemporal resolution of GEVIs is on a subcellular and millisecond scale, and is superior to that of the functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG). Further, whil...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2016.05.023
更新日期:2016-08-01 00:00:00
abstract::Immunoassays are indispensable for research and clinical analysis, and following the emergence of the omics paradigm, multiplexing of immunoassays is more needed than ever. Cross-reactivity (CR) in multiplexed immunoassays has been unexpectedly difficult to mitigate, preventing scaling up of multiplexing, limiting ass...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2013.11.012
更新日期:2014-02-01 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::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::Great progress has been made in expanding the repertoire of genetically encoded fluorescent sensors for monitoring intracellular transition metals (TMs). This powerful toolkit permits dynamic and non-invasive detection of TMs with high spatial-temporal resolution, which enables us to better understand the roles of TM ...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2017.12.002
更新日期:2018-04-01 00:00:00
abstract::The molecular mechanisms by which peptide antibiotics disrupt bacterial DNA synthesis, protein biosynthesis, cell wall biosynthesis, and membrane integrity are diverse, yet historically have been understood to follow a theme of one antibiotic, one inhibitory mechanism. In the past year, mechanistic and structural stud...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(99)00025-3
更新日期:1999-12-01 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 appearance of the highly pathogenic avian influenza virus H5N1 highlighted the potential impact of influenza virus on humanity. The emergence of this high profile virus stimulated much research towards a better understanding of the key determinants for successful human-to-human transmission and as such has provide...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2008.01.036
更新日期:2008-02-01 00:00:00
abstract::Over the past two decades, peptides have expanded the toolbox of additives for the preparation of noble metal nanoparticles. Their functional and structural modularity and accompanying molecular recognition and self-assembly properties offer unique opportunities for the controlled formation of NPs. Within this review,...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2017.09.005
更新日期:2017-10-01 00:00:00
abstract::Recent structural information suggests that the HC(X)5R active-site motif defines three distinct evolutionary families of phosphatases that employ a common catalytic mechanism. In two instances, regulation of phosphatase activity employs autoinhibitory mechanisms involving either intermolecular or intramolecular inter...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(98)80095-1
更新日期:1998-10-01 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::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::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::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
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::New insights have been gained into the formation of the di-iron tyrosyl radical cofactor, which is essential for nucleotide reduction in the class I ribonucleotide reductases. Recent advances include Insight into the function of the tyrosyl radical in initiation of nucleotide reduction. ...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(03)00025-5
更新日期:2003-04-01 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
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::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