Abstract:
:Gelatinase B/MMP-9 fulfills crucial regulator or effector functions in disease states and may be pharmacologically targeted by specific inhibitors. The characteristics of cleavages of a natural gelatinase B substrate were simulated and amino acids with zinc-ion chelating side-groups were employed to design a library of peptide-based inhibitors. Here, we extend previous findings of combinatorial chemical synthesis and subsequent library deconvolution with a recently established high-throughput technology. This enabled us to study MMP inhibitors with two zinc-binding groups and to identify a new L-pyridylalanine-containing gelatinase B inhibitor. The peptide analog was found to inhibit, almost to the same degree, the neutrophil enzymes collagenase 2/ MMP-8 and MMP-9 and the monocytic tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE/ADAM-17) in vitro and to protect mice against lethal endotoxinemia in vivo. These data illustrate the usefulness of the screening platform for protective inhibitor discovery and complement recent insights in the pathogenesis and treatment of shock syndromes.
journal_name
Comb Chem High Throughput Screenjournal_title
Combinatorial chemistry & high throughput screeningauthors
Hu J,Dubois V,Chaltin P,Fiten P,Dillen C,Van den Steen PE,Opdenakker Gdoi
10.2174/138620706778249758subject
Has Abstractpub_date
2006-09-01 00:00:00pages
599-611issue
8eissn
1386-2073issn
1875-5402journal_volume
9pub_type
杂志文章abstract:BACKGROUND AND OBJECTIVE:Perimenopause is a physiological occurrence in women, and is characterized by endocrine and biochemical changes. During perimenopause phase, many derangements or abnormal health conditions start developing as a result of hormonal changes. These derangements in health conditions and biochemical ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207323666201023120212
更新日期:2020-10-23 00:00:00
abstract::Microwave-assisted Suzuki-Miyaura and Stille cross-coupling reactions for the synthesis of highly electron-rich and diversely functionalized biaryl intermediates are presented. Microwave-irradiation has been demonstrated to be a very powerful tool for performing difficult transition metal-catalyzed cross-coupling reac...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620707783018513
更新日期:2007-11-01 00:00:00
abstract:BACKGROUND:Topological indices have numerous implementations in chemistry, biology and in lot of other areas. It is a real number associated to a graph, which provides information about its physical and chemical properties and their correlations. For a connected graph H, the degree distance defined as DD(H)=∑_(\{h_1,h_...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207323666201224123643
更新日期:2020-12-24 00:00:00
abstract::In recent years, a trend of change has been observed within pharmaceutical industry. As modern drug discovery has reached a remarkable level of complexity and drugs need to be discovered, developed and produced against strict timelines and within cost- and regulatory constraints, industry seeks "lean" solutions to inc...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章,评审
doi:10.2174/138620710791515897
更新日期:2010-07-01 00:00:00
abstract::Unfavorable oral bioavailability is an important reason accounting for the failure of the drug candidates. Considering the lack of in vitro high-throughput screening assay for oral bioavailability, it is critical to develop in silico models for early predictions of oral bioavailability. In this review, we summarize pr...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章,评审
doi:10.2174/138620711795508368
更新日期:2011-06-01 00:00:00
abstract:BACKGROUND:Clinical outcomes after rotator cuff repair associated with diabetes mellitus(DM) are generally favorable, but no study has attempted to establish the influence of DM on outcomes after rotator cuff repair. PURPOSE:To conduct a meta-analysis of clinical studies evaluating patient outcomes between people with...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: meta分析
doi:10.2174/1386207323666201020114034
更新日期:2020-10-20 00:00:00
abstract::The article describes the development of a robust pharmacophore model and the investigation of structure activity relationship analysis of 46 xanthine derivatives reported for DPP-IV inhibition using PHASE module of Schrodinger software. The present works also encompasses molecular interaction of 46 xanthine ligand th...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207311316040001
更新日期:2013-05-01 00:00:00
abstract::A biomimetic sensor is proposed as a promising new analytical method for determination of captopril in different classes of samples. The sensor was prepared by modifying a carbon paste electrode with iron (II) phthalocyanine bis(pyridine) [FePc(dipy)] complex. Amperometric measurements in a batch analytical mode were ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620710791920392
更新日期:2010-09-01 00:00:00
abstract:BACKGROUND:Panax notoginseng, a Chinese herbal medicine, has been widely used to treat vascular diseases. Diabetic retinopathy (DR) is one of the complications of diabetic microangiopathy. According to recent studies, the application of Panax notoginseng extract and related Chinese patent medicine preparations can sign...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207323666200305093709
更新日期:2020-01-01 00:00:00
abstract::Approximately 5-10% of all colorectal carcinomas arise from cancer predisposition syndromes caused by heterozygote germline mutations in post-replicative DNA mismatch repair (MMR) genes. In contrast to gastrointestinal polyposis syndromes, carcinomas in these patients do not occur on the background of increased number...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207003331409
更新日期:2000-12-01 00:00:00
abstract::We have developed high throughput fluorescence cell imaging methods to screen chemical libraries for compounds with effects on diverse aspects of cell physiology. We describe screens for compounds that arrest cells in mitosis, that block cell migration, and that block the secretory pathway. Each of these screens yield...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620703106298527
更新日期:2003-06-01 00:00:00
abstract::The GoLoco motif is a short Galpha-binding polypeptide sequence. It is often found in proteins that regulate cell-surface receptor signaling, such as RGS12, as well as in proteins that regulate mitotic spindle orientation and force generation during cell division, such as GPSM2/LGN. Here, we describe a high throughput...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620708784534770
更新日期:2008-06-01 00:00:00
abstract:AIM AND OBJECTIVE:Specific inhibitors of monoamine oxidase (MAO)-B are considered useful therapeutic agents in targeting neurological disorders like Alzheimer's and Parkinson's diseases. Due to the academic challenge of designing new hMAO-B inhibitors and the possibility of discovering compounds with improved propertie...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章,评审
doi:10.2174/1386207320666170227155517
更新日期:2017-01-01 00:00:00
abstract::Phage display is a biological system which facilitates the cloning and rapid selection of peptides from large combinatorial libraries. In compa-rison to the chemical combinatorial approach, the advantages of phage display lie in its simplicity and replicability. While phage display has many diverse applications, this ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章,评审
doi:
更新日期:1999-08-01 00:00:00
abstract::In the present work, an analytical methodology based on molecularly imprinted solid-phase extraction (MISPE) has been developed for the determination of bisphenol A (BPA) in environmental and food samples. In order to select the optimum material, a combinatorial library of molecularly imprinted polymers in small-scale...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620706779026024
更新日期:2006-12-01 00:00:00
abstract::Normalization is an essential step in microarray data mining and analysis. For cDNA microarray data, the primary purpose of normalization is removing the intensity-dependent bias across different slides within an experimental group or between multiple groups. The locally weighted regression (lowess) procedure has been...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207043328274
更新日期:2004-12-01 00:00:00
abstract:OBJECTIVE:The aim of this study areto screen MicroRNAs (miRNAs) related to the prognosis of lung adenocarcinoma (LUAD) and to explore the possible molecular mechanisms. METHODS:The data for a total of 535 patients with LUAD data were downloaded from The Cancer Genome Atlas (TCGA) database. The miRNAs for LUAD prognosi...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207323666200124123103
更新日期:2020-01-01 00:00:00
abstract::We have developed a high throughput assay for the measurement of protease activity in solution. This technology will accelerate research in functional proteomics and enable biologists to streamline protease substrate evaluation and optimization. The peptide sequences that serve as protease substrates in this assay are...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620706777698535
更新日期:2006-07-01 00:00:00
abstract::Natural products obtained from marine sources are considered to be a rich and diverse source of potential drugs. In the present work we demonstrate the use of chemoinformatics approach for the design of new molecules inspired by molecules from marine organisms. Accordingly we have assimilated information from two majo...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207318666150703112950
更新日期:2015-01-01 00:00:00
abstract::A new multicomponent domino reaction for rapid and regioselective synthesis of highly functionalized benzo[h]naphtho[2,3-a]acridine-15,16(5H,14H)-diones has been established. The reaction can be conducted by using readily available and inexpensive substrates under microwave irradiation. The procedures are facile, avoi...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620712800194459
更新日期:2012-06-01 00:00:00
abstract::African trypanosomes are extracellular blood parasites that cause sleeping sickness in humans and Nagana in cattle. The therapeutics used to control and treat these diseases are very ineffective and thus, the development of new drugs is urgently needed. We have previously suggested to use trypanosome-specific RNA apta...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620706777935324
更新日期:2006-08-01 00:00:00
abstract::Recently, we established a robust method for the detection of hybridization events using a DNA microarray deposited on a nanoporous membrane. Here, in a follow-up study, we demonstrate the performance of this approach on a larger set of LNA-modified oligoprobes and genomic DNA sequences. Twenty-six different LNA-modif...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620707780636637
更新日期:2007-05-01 00:00:00
abstract::Most essential functions are associated with various protein-protein interactions, particularly the cytokine-receptor interaction. Knowledge of the heterogeneous network of cytokine- receptor interactions provides insights into various human physiological functions. However, only a few studies are focused on the compu...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207319666151110122621
更新日期:2016-01-01 00:00:00
abstract::Direct renin inhibitors (DRIs) have increasingly shown a significant advantage in the treatment of hypertension and protection of target organs. In this paper, a series of azaindole class renin inhibitors were subjected to 3D-QSAR study using Topomer CoMFA. Five kinds of splitting mode for different fragment cutting a...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207317666140107094708
更新日期:2014-01-01 00:00:00
abstract::A comparative structure-affinity study of anthraquinone dyes adsorption on cellulose fibre is presented in this paper. We used receptor-dependent 4D-QSAR methods based on grid and neural (SOM) methodology coupled with IVEPLS procedure. The applied RD 4D-QSAR approach focuses mainly on the ability of mapping dye proper...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207317666140205195252
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Considering the low ocular bioavailability of conventional formulations used for ocular bacterial infection treatment, there's a need for designing efficient novel drug delivery systems that may enhance of precorneal retention time and corneal permeability. AIM AND OBJECTIVE:The current research focuses on ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207323666200428091945
更新日期:2020-04-27 00:00:00
abstract::Two approaches were utilized to increase the throughput of pulsed ultrafiltration assays of ligand binding to human serum albumin, reducing the volume of the ultrafiltration chamber and combining pulsed ultrafiltration with high performance liquid chromatography-atmospheric pressure chemical ionization mass spectromet...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:
更新日期:1999-12-01 00:00:00
abstract::We describe a high-throughput, quantitative technology for fast identification of all different clones present in selectively enriched phage surface-displayed cDNA libraries. The strategy is based on a combination of phage display and high-density arrays. To demonstrate the utility of the method cDNAs of Aspergillus f...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207033329751
更新日期:2003-03-01 00:00:00
abstract:BACKGROUND:Camptothecin is a quinoline alkaloid, isolated from the Chinese tree Camptotheca acuminate which exhibits its cytotoxic activity by the inhibition of nuclear enzyme Topoisomerase I (topo I). Camptothecin and its analogues forms a covalent bond with DNA which can arrest the tumor growth by slowing the religat...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207319666160810154346
更新日期:2016-01-01 00:00:00
abstract:AIM AND OBJECTIVE:Lysine acetylation, as one type of post-translational modifications (PTM), plays key roles in cellular regulations and can be involved in a variety of human diseases. However, it is often high-cost and time-consuming to use traditional experimental approaches to identify the lysine acetylation sites. ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207320666170314093216
更新日期:2017-01-01 00:00:00