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 costly combination with proguanil (Malarone), limiting its widespread use in resource-poor disease-endemic areas. Cheaper alternatives that can overcome resistance are desperately required. Here we describe recent advances of bc(1)-targeted inhibitors that include hydroxynaphthoquinones (atovaquone analogues), pyridones (clodipol analogues), acridine related compounds (acridinediones and acridones) and quinolones. Significantly, many of these developmental compounds demonstrate little cross resistance with atovaquone-resistant parasite strains, and selected classes have excellent oral activity profiles in rodent models of malaria.
journal_name
Curr Opin Chem Bioljournal_title
Current opinion in chemical biologyauthors
Barton V,Fisher N,Biagini GA,Ward SA,O'Neill PMdoi
10.1016/j.cbpa.2010.05.005subject
Has Abstractpub_date
2010-08-01 00:00:00pages
440-6issue
4eissn
1367-5931issn
1879-0402pii
S1367-5931(10)00068-2journal_volume
14pub_type
杂志文章,评审abstract：:Fragment-based screening has now become an established method for the generation of lead molecules against therapeutic targets. Fragment molecules are simple, low molecular-weight compounds with few chemical functionalities. These characteristics lead to high hit rates for fragment screening as compared to the more cl...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2011.02.020
更新日期：2011-08-01 00:00:00
abstract：:Oligonucleotide in vitro selection provides surprisingly specific aptamers to protein targets. Synthetic chemistries for modifying nucleotides have been developed to enhance aptamer binding affinity. The diversity of nucleosides amenable to either triphosphate synthesis or phosphoramidite activation is now sufficientl...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(97)80103-2
更新日期：1997-06-01 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
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：: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：:Covalent attachment of glycosylphosphatidylinositols (GPIs) to the protein C-terminus is one of the most common posttranslational modifications in eukaryotic cells. In addition to anchoring surface proteins to the cell membrane, GPIs also have many other important biological functions, determined by their unique struc...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2013.09.016
更新日期：2013-12-01 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：: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：:The area of lipid molecular design is attracting widespread interest among numerous research groups worldwide. Diverse lipid assemblies in aqueous media, such as vesicles, bilayers and nanorods, offer new applications in chemical biology. Lipids with specifically tailored molecular architecture have been successfully ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2005.10.016
更新日期：2005-12-01 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：:Lipids are indispensable cellular building blocks, and their post-translational attachment to proteins makes them important regulators of many biological processes. Dysfunction of protein lipidation is also implicated in many pathological states, yet its systematic analysis presents significant challenges. Thanks to i...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2020.10.002
更新日期：2020-11-19 00:00:00
abstract：:Fifty years after the publication of the DNA double helix model by Watson and Crick, new nucleic acid structures keep emerging at an ever-increasing rate. The past three years have brought a flurry of new oligonucleotide structures, including those of a Hoogsteen-paired DNA duplex, Holliday junctions, DNA-drug complex...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2004.09.004
更新日期：2004-12-01 00:00:00
abstract：:Four-electron reduction of dioxygen to water and splitting of water to dioxygen are extremely important processes in the context of attaining clean renewable energy sources. High-valent metal-oxo cores are proposed as reactive intermediates in these vital processes, although they have only been isolated in extremely r...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2015.01.014
更新日期：2015-04-01 00:00:00
abstract：:New catalysts and reaction conditions have been developed for the dynamic kinetic resolution or deracemisation of racemic mixtures of chiral compounds. Specific functional groups that lend themselves particularly well to this approach include chiral secondary alcohols, alpha-amino acids, amines and carboxylic acids. A...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2004.02.001
更新日期：2004-04-01 00:00:00
abstract：:The manufacture and use of protein microarrays with correctly folded and functional content presents significant challenges. Despite this, the feasibility and utility of such undertakings are now clear, and exciting progress has recently been demonstrated in the areas of content generation, printing strategies and pro...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2003.12.005
更新日期：2004-02-01 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：: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：: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：:Amide forming reactions are central to the field of peptide and protein synthesis and are considered to be poorly reversible reactions owing to the high stability of peptide bonds. One amide-forming reaction is native chemical ligation (NCL) which is driven by a sulfur to nitrogen acyl migration process from a transie...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2014.09.030
更新日期：2014-10-01 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：: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：: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：: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：:The design of dimeric coiled-coils has ultimately led to novel applications, such as self-replicating peptide systems, whereas the structural features of the less common trimeric coiled-coil continue to be elucidated. Novel topologies have been discovered in designed proteins, as exemplified by the right-handed tetram...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(99)00031-9
更新日期：1999-12-01 00:00:00
abstract：:The principles of enzyme chemistry, mechanism of action and inhibitor design are being applied to proteomics by the development of activity-based probes. This approach suggests a potentially broad method for interrogating enzyme family members, both known and unknown, in cells and proteomic fractions without the need ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(02)00013-3
更新日期：2003-02-01 00:00:00
abstract：:During the past year, remarkable progress has been made in understanding how periplasmic chaperones fold and protect protein modules that are destined for assembly into adhesive pili in Gram-negative bacteria. The first two three-dimensional structures of complexes of periplasmic chaperones with substrate pilus subuni...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(00)00144-7
更新日期：2000-12-01 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：: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：:The active site of cross-linked enzyme crystals can be further modified by chemical means, yielding a new type of chemically engineered enzyme. In the past year, the characteristics of cross-linked protein crystals as microporous materials have been studied and used as stationary phases in chromatographic separations....
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(99)80007-6
更新日期：1999-02-01 00:00:00
abstract：:In recent years, an increasing number of proteins have been discovered which utilize heme cofactors to sense oxygen, carbon monoxide and nitric oxide. The identification and characterization of these proteins are revising our understanding of heme-mediated allostery first established in the early 1960s. Biochemical an...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(00)00193-9
更新日期：2001-04-01 00:00:00
