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 inspiration for scaffolds and reagents are all areas of progressive research.
journal_name
Curr Opin Chem Bioljournal_title
Current opinion in chemical biologyauthors
Rose S,Stevens Adoi
10.1016/s1367-5931(03)00057-7subject
Has Abstractpub_date
2003-06-01 00:00:00pages
331-9issue
3eissn
1367-5931issn
1879-0402pii
S1367593103000577journal_volume
7pub_type
杂志文章,评审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::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
doi:10.1016/s1367-5931(99)00014-9
更新日期:1999-10-01 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 eukaryotic ribonucleoprotein reverse transcriptase (RT) telomerase uses a template within its integral RNA subunit to extend chromosome ends by synthesis of single-stranded telomeric repeats. Telomerase is adapted to its unique cellular role by an ability to release product DNA in single-stranded form, regeneratin...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2011.07.011
更新日期:2011-10-01 00:00:00
abstract::The chemokines are a large superfamily of chemotactic cytokines that are utilized to direct the trafficking and migration of leukocytes within the immune system. The chemokines mediate their activity through a large family of G-protein-coupled receptors, and thus are highly tractable as therapeutic targets. Exciting a...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(00)00113-7
更新日期:2000-08-01 00:00:00
abstract::Structural genomics (SG) has significantly increased the number of novel protein structures of targets with medical relevance. In the protein kinase area, SG has contributed >50% of all novel kinases structures during the past three years and determined more than 30 novel catalytic domain structures. Many of the relea...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2008.01.042
更新日期:2008-02-01 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::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::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::The biosynthetic pathways of plant natural products offer an abundance of knowledge to scientists in many fields. Synthetic chemists can be inspired by the synthetic strategies that nature uses to construct these compounds. Chemical and biological engineers are working to reprogram these biosynthetic pathways to more ...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2009.06.019
更新日期:2009-10-01 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::Some therapeutic monoclonal antibodies function by focusing the killing power of the immune system on particular cellular targets, a process known as antibody-dependent cell-mediated cytotoxicity (ADCC). There is considerable interest in developing small-molecule therapeutics that utilize this mechanism of action and ...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2010.07.002
更新日期:2010-12-01 00:00:00
abstract::New insights have been gained into the therapeutic relevance of the sphingosine 1-phosphate (S1P) pathway, on the basis of reverse pharmacological approaches to defining the mechanism of action of the immunosuppressive agent FTY720. Natural and synthetic sphingosine 1-phosphate receptor agonists can make picomolar int...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(03)00085-1
更新日期:2003-08-01 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::There has been a significant increase in the number of compounds synthesized in early drug-discovery programs with the advances in combinatorial chemistry and high-throughput biological screening efforts. Various in silico, in vitro and in situ approaches have been described in literature that achieve higher throughpu...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(00)00228-3
更新日期:2001-08-01 00:00:00
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
pub_type: 杂志文章,评审
doi:10.1016/S1367-5931(99)80071-4
更新日期:1999-08-01 00:00:00
abstract::Recently, the hypothesis that protein motions are involved in enzymatic turnover has gained significant attention. We review cases where there is evidence that protein motions are rate-limiting in the overall catalytic cycle and examine experimental and theoretical evidence for how such motions enhance the probability...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2010.07.020
更新日期:2010-10-01 00:00:00
abstract::Oligosaccharyl transferase is part of the macromolecular machinery that processes nascent proteins in the endoplasmic reticulum. The enzyme is highly conserved, catalyzes the initial step in the biosynthesis of N-linked glycoproteins and acts as a 'gatekeeper' for the secretory pathway. As more proteins associated wit...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(02)00390-3
更新日期:2002-12-01 00:00:00
abstract::The introduction of fluorine atoms into organic molecules has received considerable attention as these organofluorines have often found widespread applications in bioorganic chemistry, medicinal chemistry and biomaterial science. Despite innovation of synthetic C-F forming methodologies, selective fluorination is stil...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2020.01.004
更新日期:2020-04-01 00:00:00
abstract::Metal ions are known to act as catalytic centres in metallo-enzymes. On the other hand, low-molecular-weight metal complexes are widely used as catalysts in chemical systems. However, small catalysts do not have a large protein ligand to provide substrate selectivity and minimize catalyst poisoning. Despite the challe...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2015.01.024
更新日期:2015-04-01 00:00:00
abstract::In the past five to ten years, it has become increasingly apparent that the function of Fe-S clusters is not limited to electron transfer, a function implicit in their discovery. We now know that the vulnerability of these structures to oxidative destruction is used by nature in sensing O2, iron, and possibly also nit...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/S1367-5931(99)80027-1
更新日期:1999-04-01 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::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::In recent years pharmaceutical companies have utilized structure-based drug design and combinatorial library design techniques to speed up their drug discovery efforts. Both approaches are routinely used in the lead discovery and lead optimization stages of the drug discovery process. Fragment-based drug design, a new...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2008.02.007
更新日期:2008-06-01 00:00:00
abstract::Chromatin, the nucleoprotein complex organizing the genome, is central in regulating gene expression and genome organization. Chromatin conformational dynamics, controlled by histone post-translational modifications (PTM) and effector proteins, play a key role in this regulatory function. Recent developments in chemic...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2019.01.022
更新日期:2019-08-01 00:00:00
abstract::Altered metabolite levels can drive epigenetic changes critical to development and disease. However, in many cases the specific protein-metabolite interactions that underlie this process remain enigmatic. In this review, we make the case that this fundamental missing information may be discovered by applying the tools...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2019.02.002
更新日期:2019-08-01 00:00:00
abstract::The role of integrin and extracellular matrix proteins in various pathological processes (including angiogenesis, thrombosis, apoptosis and cell migration and proliferation), leading to both acute and chronic disease states (e.g. ocular diseases, metastasis, unstable angina, myocardial infarction, stroke, osteoporosis...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(02)00350-2
更新日期:2002-08-01 00:00:00
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 mecha...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2012.12.022
更新日期:2013-02-01 00:00:00
abstract::Self-assembled monolayer (SAM) and fluorescent quantum dots (QDs) share common ground as emerging tools for nanoscale observation of biological interactions. SAMs provide excellent means of controlling the surface characteristics through individually tailored and engineered building blocks. SAMs on various surfaces ha...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2006.08.006
更新日期:2006-10-01 00:00:00
abstract::RNA plays an essential cellular role in nearly every aspect of the transmission and expression of genetic information, including regulatory roles that have significance for cellular development. Access to RNA bearing synthetic modifications has allowed biological chemists to probe deep into the inner workings of cellu...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2005.10.009
更新日期:2005-12-01 00:00:00