共查询到20条相似文献,搜索用时 31 毫秒
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RNases are important enzymes of cell metabolism, influencing gene expression, affecting cell growth and differentiation, and participating in cell defense against pathogens and induction of apoptosis. Since RNases mostly occur in complex with their inhibitors in the cell, the inhibitors also play a role in the above processes. The review considers natural protein RNase inhibitors of animals, plants, and bacteria, as well as synthetic low-molecular-weight inhibitors. Special emphasis is placed on the prospective use of RNase inhibitors in the therapy of cancer and allergy. While RNases are widespread, the number of the available natural and synthetic inhibitors is limited. A pressing problem is to design highly effective low-molecular-weight inhibitors of the RNase activity of angiogenin and eosinophil-associated RNases for anticancer and antiallergy therapy. 相似文献
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Summary The effects of furano compounds, furfural (furfuraldehyde) and furfuryl alcohol (5, 10, 20 and 30% of N applied) on nitrification of ammonium sulfate and urea N were studied in a sandy clay loam in laboratory. Both furfural and furfuryl alcohol significantly retarded the nitrification rates of both the fertilizers by inhibiting the conversion of NH4
+ to NO2
- without affecting the oxidation of NO2
- to NO3
--N. 10, 20 and 30% concentrations of the compounds were effective up to 75 days with ammonium sulfate but more or less up to 45 days with urea. re]19760322 相似文献
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Caspase inhibitors 总被引:10,自引:0,他引:10
Caspases are the key effector molecules of the physiological death process known as apoptosis, although some are involved in activation of cytokines, rather than cell death. They exist in most of our cells as inactive precursors (zymogens) that kill the cell once activated. Caspases can be controlled in two ways. The processing and activation of a caspase can be regulated by molecules such as FADD, APAF-1, Bcl-2 family members, FLIP and IAPs. Active caspases can be controlled by a variety of inhibitors that directly interact with the protease. This review describes the later direct caspase inhibitors that have been identified, products of both viral and cellular genes, and artificial caspase inhibitors that have been developed both as research tools and as pharmaceutical agents to inhibit cell death in vivo. 相似文献
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The Botanical Review - The presence of germination-inhibiting substances in plants seems to be a wide-spread phenomenon. They occur in all parts of plants —in fruit pulp, fruit coats,... 相似文献
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Telomerase inhibitors 总被引:19,自引:0,他引:19
There has been a vast increase in telomerase research over the past several years, with many different pre-clinical approaches being tested for inhibiting the activity of this enzyme as a novel therapeutic modality to treat malignancy. In this review, we will provide some basic background information about telomeres and telomerase and then discuss the pros, cons and challenges of the approaches that are currently under investigation, and what we might expect in the future of this emerging field. 相似文献
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Aminopeptidases are enzymes that selectively hydrolyze an amino acid residue from the N-terminus of proteins and peptides. They are important for the proper functioning of prokaryotic and eukaryotic cells, but very often are central players in the devastating human diseases like cancer, malaria and diabetes. The largest aminopeptidase group include enzymes containing metal ion(s) in their active centers, which often determines the type of inhibitors that are the most suitable for them. Effective ligands mostly bind in a non-covalent mode by forming complexes with the metal ion(s). Here, we present several approaches for the design of inhibitors for metallo-aminopeptidases. The optimized structures should be considered as potential leads in the drug discovery process against endogenous and infectious diseases. 相似文献
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Cherney RJ King BW Gilmore JL Liu RQ Covington MB Duan JJ Decicco CP 《Bioorganic & medicinal chemistry letters》2006,16(4):1028-1031
Novel sultam hydroxamates with potent MMP activity were transformed into potent TACE inhibitors, lacking MMP activity. To accomplish this we relied on structural differences between the MMP and TACE S1' pockets and the known advantageous fit of a 2-methyl-4-quinolinylmethoxyphenyl group into this region. From this approach, compound 7d was identified as a potent TACE inhibitor (IC50 = 3.7 nM) that lacked MMP-1, -2, -9, and -13 activity. 相似文献
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A D Elbein 《FASEB journal》1991,5(15):3055-3063
The biosynthesis of the various types of N-linked oligosaccharide structures involves two series of reactions: 1) the formation of the lipid-linked saccharide precursor, Glc3Man9(GlcNAc)2-pyrophosphoryl-dolichol, by the stepwise addition of GlcNAc, mannose and glucose to dolichyl-P, and 2) the removal of glucose and mannose by membrane-bound glycosidases and the addition of GlcNAc, galactose, sialic acid, and fucose by Golgi-localized glycosyltransferases to produce different complex oligosaccharide structures. For most glycoproteins, the precise role of the carbohydrate is still not known, but specific N-linked oligosaccharide structures are key players in targeting of lysosomal hydrolases to the lysosomes, in the clearance of asialoglycoproteins from the serum, and in some cases of cell:cell adhesion. Furthermore, many glycoproteins have more than one N-linked oligosaccharide, and these oligosaccharides on the same protein frequently have different structures. Thus, one oligosaccharide may be of the high-mannose type whereas another may be a complex chain. One approach to determining the role of specific structures in glycoprotein function is to use inhibitors that block the modification reactions at different steps, causing the cell to produce glycoproteins with altered carbohydrate structures. The function of these glycoproteins can then be assessed. A number of alkaloid-like compounds have been identified that are specific inhibitors of the glucosidases and mannosidases involved in glycoprotein processing. These compounds cause the formation of glycoproteins with glucose-containing high mannose structures, or various high-mannose or hybrid chains, depending on the site of inhibition. These inhibitors have also been useful for studying the processing pathway and for comparing processing enzymes from different organisms. 相似文献
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So far the Cl inactivator, alpha 2-macroglobulin, antithrombin III (in the presence of heparin), and alpha 1-antitrypsin have been identified as inhibitors of plasma kallikrein; alpha 1-antitrypsin reacts slowly also with tissue kallikreins. Of the various naturally occurring kallikrein inhibitors the basic trypsin-kallikrein inhibitor of bovine organs, aprotinin (the active substance of Trasylol), has attained by far the most interest. This inhibitor, which is produced by mast cells, has unusual properties due to its compact tertiary structure. Additional topics of aprotinin and structurally related inhibitors discussed are the mechanism of enzyme-inhibitor complex formation, the production of chemical mutants of aprotinin, the structural basis of kallikrein inhibition, and selected aspects regarding aprotinin medication. 相似文献
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A S Bhatnagar A H?usler K Schieweck L J Browne R Bowman R E Steele 《The Journal of steroid biochemistry and molecular biology》1990,37(3):363-367
Aminoglutethimide (AG), an inhibitor of the aromatase enzyme, inhibits the biosynthesis of estrogens and displays well-documented anti-tumor efficacy in breast-cancer. However, this efficacy is accompanied by a relative lack of specificity in inhibiting aromatase and moderate tolerability. We report on two new non-steroidal aromatase inhibitors (CGS 16949A and CGS 18320B) which are more potent, selective and efficacious in their inhibition of aromatase than AG. Both compounds inhibit aromatase more potently in vitro and in vivo (over 400 and 1000 times respectively) than AG. They are both more selective in their inhibition of aromatase with CGS 18320B showing an improved selectively over CGS 16949A. When administered to adult female rats, both compounds elicit responses in serum hormones similar to those seen after ovariectomy. The duration of action of CGS 18320B, however, appears to be longer than that of CGS 16949A. CGS 18320B and CGS 16949A cause almost complete regression of DMBA-induced mammary tumors in adult female rats and almost completely suppress the appearance of new tumors. Thus CGS 16949A and CGS 18320B represent significant advances in the search for novel aromatase inhibitors which are more potent, selective and efficacious than aminoglutethimide. 相似文献
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Tyrosine hydroxylase inhibitors 总被引:4,自引:0,他引:4
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Chen Z Kim SH Barbosa SA Huynh T Tortolani DR Leavitt KJ Wei DD Manne V Ricca CS Gullo-Brown J Poss MA Vaccaro W Salvati ME 《Bioorganic & medicinal chemistry letters》2006,16(3):628-632
The synthesis and SAR of a series of pyrrolopyridazine MEK inhibitors are reported. Optimal activity was achieved by incorporation of a 4-phenoxyaniline substituent at C4 and an acylated amine at C6. 相似文献
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Claudiu T. Supuran 《Bioorganic & medicinal chemistry letters》2010,20(12):3467-3474
Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread enzymes in all organisms, catalyzing CO2 hydration to bicarbonate and protons. Their inhibition is exploited clinically for decades for various classes of diuretics and systemically acting antiglaucoma agents. In the last years novel applications of CA inhibitors (CAIs) emerged, such as topically acting antiglaucoma, anticonvulsants, antiobesity, antipain, and antitumor agents/diagnostic tools. Such CAIs target diverse isozymes of the 13 catalytically active α-CA isoforms present in mammals. CAs belonging to the α-, β-, γ-, δ-, and ζ-families are found in many organisms all over the phylogenetic tree, and their inhibition was studied ultimately for some pathogenic protozoa (Plasmodium falciparum), fungi (Cryptococcus neoformans, Candida albicans, Candida glabrata, and Saccharomyces cerevisiae), and bacteria (Helicobacter pylori, Mycobacterium tuberculosis, and Brucella suis). Novel interesting chemotypes, in addition to the sulfonamide and sulfamate CAIs, such as coumarins, phenols, and fullerenes, were also reported recently, together with their mechanism of inhibition. This class of enzyme inhibitors shows promise for designing interesting pharmacological agents and understanding in detail protein–drug interactions at molecular level. 相似文献
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