Abstract:
:This article is a review with 83 references of the application of NMR to the measurement of the dissociation constants of protein-ligand complexes. After briefly discussing some general concepts of molecular stability, the text turns to consider which NMR parameters are reporters of complex formation. The available data treatments required to translate observed NMR effects into quantitative measurements of the stability of the complex in the form of the dissociation constant (KD) are introduced. Linearisation methods and curve fitting methods are explained in detail and are illustrated with examples drawn from recent reports of protein-small molecule interactions. Throughout the text examples of the commonly observed NMR parameters , 1 / T1 and 1 / T2 are drawn from biological studies of 1H, 31P, 19F 15N (and other nuclei). The advantages of NMR diffusion experiments as a measure of KD are considered. Some less frequently used NMR approaches, some new ideas and some non-general methods are grouped together in a miscellaneous section. The major sources of errors in the determination of KD are identified. This allows recommendations for optimal experimental set up. Options for dealing with strong binding are reviewed. Finally, the implications of abstracting KD data from high throughput screening experiments are considered and several different approaches to generate this data are discussed.
journal_name
Curr Top Med Chemjournal_title
Current topics in medicinal chemistryauthors
Fielding Ldoi
10.2174/1568026033392705keywords:
subject
Has Abstractpub_date
2003-01-01 00:00:00pages
39-53issue
1eissn
1568-0266issn
1873-4294journal_volume
3pub_type
杂志文章,评审abstract::G protein coupled receptors (GPCRs) are membrane proteins coupled with G proteins through which they transmit signals to the cytoplasm. Approximately 30% of pharmaceuticals target these receptors, even though crystal structures were scarce at the time. Furthermore, an additional 15% of GPCRs have yet to be exploited f...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026615666150915121324
更新日期:2016-01-01 00:00:00
abstract::A modified version of the CORAL software (http://www.insilico.eu/coral) allows building up the classification model for the case of the Yes/No data on the anti-sarcoma activity of organic compounds. Three random splits into the sub-training, calibration, and test sets of the data for 3017 compounds were examined. The ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026611212240004
更新日期:2012-01-01 00:00:00
abstract::In the last decade, we have been developing some gold(III) derivatives showing interesting antitumor properties and reduced systemic and renal toxicity, compared to the clinically-established reference drug cisplatin. Starting from the rationale at the base of our investigations, this review has been divided into two ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026615666150827094500
更新日期:2016-01-01 00:00:00
abstract::Parkinson's disease (PD) is one of the most prevalent and severe neurodegenerative disease affecting more than 6.1 million people globally. It is characterized by age-related progressive deterioration of neurological functions caused by neuronal damage or neuronal death. During PD, the dopamineproducing cells in the s...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026620666201019112557
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Nowadays, malaria is still one of the most important and lethal diseases worldwide, causing 445,000 deaths in a year. Due to the actual treatment resistance, there is an emergency to find new drugs. OBJECTIVE:The aim of this work was to find potential inhibitors of phosphoglycerate mutase 1 from P. falcipar...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026618666181029144653
更新日期:2018-01-01 00:00:00
abstract::The chemical versatility of the indole nucleus still inspires the pharmaceutical research to develop innovative suitable indole based drugs. The present work is an overview of the use and application of indole molecule based derivatives, as possible treatment in the main Oxidative Stress related diseases, such as card...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026614666141203142926
更新日期:2014-01-01 00:00:00
abstract::Transient Receptor Potential (TRP) cation channels participate in several processes of vital importance in cell and organism physiology, and have been demonstrated to participate in the detection of sensory stimuli. The thermo TRP's reviewed: TRPV1 (vanilloid 1), TRPM8 (melastatin 8) and TRPA1 (ankyrin-like 1) are kno...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802611796904870
更新日期:2011-01-01 00:00:00
abstract::Fluorine-18 ((18)F, beta(+); 96.7%, T(1/2)=109.8 min) is of considerable importance for developing positron emission tomography (PET) ligands for imaging receptor, enzyme, gene expression etc. in brain, tumor, myocardium and other regions or organs due to its optimal decay characteristics. To synthesize (18)F-labeled ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802607782507448
更新日期:2007-01-01 00:00:00
abstract::The problem in this work is the computational characterization of cyclodextrins, crown ethers and hyaluronan (HA) as hosts of inclusion complexes for nanosized drug delivery vehicles in pharmaceutical formulations. The difficulty is addressed through a computational study of some thermodynamic, geometric and topologic...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026615666150506145619
更新日期:2015-01-01 00:00:00
abstract::A major strategy used in drug design is the inhibition of enzyme activity. The ability to accurately measure the concentration of the inhibitor which is required to inhibit a given biological or biochemical function by half is extremely important in ranking compounds. Since the concept of the half maximal inhibitory c...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802612800672844
更新日期:2012-01-01 00:00:00
abstract::Lipoic acid (LA) is an antioxidant able to produce its effects in aqueous or lipophilic environments. Lipoate is the conjugate base of lipoic acid, and the most prevalent form of LA under physiological conditions. It presents a highly negative reduction potential, increases the expression of antioxidant enzymes and pa...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026615666150114161358
更新日期:2015-01-01 00:00:00
abstract::Escherichia coli purine nucleoside phosphorylase (PNP) catalyzes the cleavage of 9-(2-deoxy-beta-D-ribofuranosyl)-6-methylpurine (MeP-dR), while human PNP does not. MeP-dR is well tolerated while the cleavage product, 6-methylpurine (MeP), is highly cytotoxic. This clinical profile suggests an anticancer gene therapy ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802605774463105
更新日期:2005-01-01 00:00:00
abstract::Anticancer drug screening can accelerate drug discovery to save the lives of cancer patients, but cancer heterogeneity makes this screening challenging. The prediction of anticancer drug sensitivity is useful for anticancer drug development and the identification of biomarkers of drug sensitivity. Deep learning, as a ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026620666200710101307
更新日期:2020-01-01 00:00:00
abstract::A major neurotransmitter, L-Glutamate must be stored, transported and received, and these processes are mediated by proteins that bind this simple yet essential amino acid. Detailed evidence continues to emerge on the structure of Glu binding proteins, which includes both receptors and transporters. It appears that re...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802606777057535
更新日期:2006-01-01 00:00:00
abstract::Pronucleotides represent a promising alternative to improve the biological activity of nucleoside analogues against different viral diseases. The basic idea is to achieve nucleotide delivery into cells, bypassing limitations with intracellular formation of nucleotides from their nucleoside precursors. The cycloSal-con...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026023393183
更新日期:2002-10-01 00:00:00
abstract::There exists a huge attrition rate of molecules in clinical trials. It was expected that high-throughput screening and combinatorial chemistry would make the task of producing drugs easier. However, the efforts of the past decade have not been an unvarnished success. As a result, a lot of experimental and computationa...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026023392968
更新日期:2002-12-01 00:00:00
abstract::This review describes the role of nuclear receptors in the regulation of genes involved in cholesterol transport and synthetic modulators of these receptors. Increasing the efflux of cholesterol from peripheral cells, such as lipid-laden macrophages, through a process called reverse cholesterol transport (RCT) require...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026053544588
更新日期:2005-01-01 00:00:00
abstract::Four compounds (isoquercitrin, myricetin-3-O-glucoside, catechin and gallocatechin) were isolated from lyophilized aqueous extract of Schizolobium parahyba leaves by chromatography on Sephadex LH-20, followed by semipreparative HPLC using a C-18 column, and identified by 1H and 13C NMR. The compounds were then, tested...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/156802611797633438
更新日期:2011-01-01 00:00:00
abstract::Inflammation is a complex phenomenon necessary in human defense mechanisms but also involved in the development of some human diseases. The discovery of cyclooxygenase-2 (COX- 2) improved the pharmacology of nonsteroidal anti-inflammatory drugs (NSAID) giving a clear mechanism for prostaglandin regulation in vivo and ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026617666170821124947
更新日期:2017-01-01 00:00:00
abstract::The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally α-amino acids with one or more stereogenic centers due to st...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802611795164990
更新日期:2011-01-01 00:00:00
abstract::The treatment and prevention of atrial fibrillation (AF) remains a significant unmet medical need. Existing therapies that maintain or restore sinus rhythm (rhythm control) have deleterious effects on the ventricle. A major goal for finding new AF therapies is the identification of repolarization mechanisms that are p...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802609788340832
更新日期:2009-01-01 00:00:00
abstract::Angiotensin II (AII), Asp1-Arg2-Val3-Tyr4-Ile5-His6-Pro7-Phe8, the primary active hormone of the Renin-Angiotensin-System (RAS), is a major vasoconstrictor implicated in the cause of hypertension. To unravel the question of the biologically active conformation(s) of this flexible peptide hormone and to better understa...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026043451375
更新日期:2004-01-01 00:00:00
abstract::The use of vaccines has led to tremendous decreases in disease burdens across the world. Many challenges remain in expanding vaccine coverage to new pathogens, however, a struggle further hampered by a lack of understanding into many of the fundamental processes through which vaccines elicit robust immunity. In this r...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/15680266113136660185
更新日期:2013-01-01 00:00:00
abstract::This is a general review of currently available antimalarial drugs, these compounds are gathered according with its chemical structure and the biological targets. A great number of these new antimalarial agents are now moving actively in the pipeline from basic science to clinical studies. ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026023392986
更新日期:2002-11-01 00:00:00
abstract::Schizophrenia (SZ) is a severe neuropsychiatric disorder. A leading hypothesis is that SZ is a brain dysconnection syndrome, involving abnormal interactions between widespread brain networks. Resting state functional magnetic resonance imaging (R-fMRI) is a powerful tool to explore the dysconnectivity of brain network...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802612805289890
更新日期:2012-01-01 00:00:00
abstract::Penile erection is a complex physiologic event resulting from the interactions of the nervous system on a highly specialized vascular organ. Activation of central nervous system melanocortinergic (MC) receptors with either endogenous or synthetic melanotropic ligands may initiate and/or facilitate spontaneous penile e...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
abstract::The adenosine A(2A) receptor is a member of the G protein-coupled receptor family and mediates multiple physiological effects of adenosine, both at the central nervous system and at peripheral tissues. Increasing evidence relates the A(2A) receptor with several pathological conditions such as neurodegenerative disorde...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802610791268765
更新日期:2010-01-01 00:00:00
abstract::Traditionally the role of sexual steroid hormones was focused primarily on reproductive organs: the breast, female reproductive tract (uterus, mammary gland, and ovary), and male reproductive tract (testes, epididymis and prostate), however our current understanding of tissue-specific effects of sex steroids has eluci...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802611796117540
更新日期:2011-01-01 00:00:00
abstract::The knowledge about to which biomolecules a small molecule binds is highly valuable in the drug development process. Although analytical methods to dissect ligand-binding proteome have made substantial progress in the past decades, it is generally too costly, if not infeasible, to know where a small molecule binds at ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802612804547362
更新日期:2012-01-01 00:00:00
abstract::Pyridine and pyridine-fused ring systems are ubiquitous in medicinal research and demonstrate such diverse pharmacological benefits as anticonvulsant therapies, treatment for fungal and bacterial infections as well as chemotherapy agents. For example, imidazo[1,2-a]pyridines have exhibited a broad range of activity as...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026616666160506145141
更新日期:2016-01-01 00:00:00