Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sites of glycosylation of Chinese hamster ovary cell expressed testicular angiotensin-converting enzyme (tACE) have been determined by matrix-assisted laser desorption ionization/time of flight/mass spectrometry of peptides generated by proteolytic and cyanogen bromide digestion. Two of the seven potential N-linked glycosylation sites, Asn90 and Asn109, were found to be fully glycosylated by analysis of peptides before and after treatment with a series of glycosidases and with endoproteinase Asp-N. The mass spectra of the glycopeptides exhibit characteristic clusters of peaks which indicate the N-linked glycans in tACE to be mostly of the biantennary, fucosylated complex type. This structural information was used to demonstrate that three other sites, Asn155, Asn337, and Asn586, are partially glycosylated, whereas Asn72 appears to be fully glycosylated. The only potential site that was not modified is Asn620. Sequence analysis of tryptic peptides obtained from somatic ACE (human kidney) identified six glycosylated and one unglycosylated Asn. Only one of these glycosylation sites had a counterpart in tACE. Comparison of the two proteins reveals a pattern in which amino-terminal N-linked sites are preferred. The functional significance of glycosylation was examined with a tACE mutant lacking the O-glycan-rich first amino-terminal 36 residues and truncated at Ser625. When expressed in the presence of the alpha-glucosidase I inhibitor N-butyldeoxynojirimycin and treated with endoglycosidase H to remove all but the terminal N-acetylglucosamine residues, it retained full enzymatic activity, was electrophoretically homogeneous, and is a good candidate for crystallographic studies.
...
PMID:Identification of N-linked glycosylation sites in human testis angiotensin-converting enzyme and expression of an active deglycosylated form. 901 98

The design, synthesis, and biochemical profile of meta-substituted benzofused macrocyclic lactams are described. The meta-substituted benzofused macrocyclic lactams were designed to have a degree of flexibility allowing the amide bond to occupy two completely different conformations while maintaining sufficient rigidity to allow for strong interaction between enzyme and inhibitor. Using TFIT, a novel molecular superimposition program, it was shown that the meta analogs could be readily superimposed onto our ACE inhibitor template whereas no low-energy superimpositions of the ortho-substituted macrocycles could be found. The macrocycles were prepared by tethering aldehyde 1 derived from S-glutamic acid or S-aspartic acid to a meta-substituted phosphonium bromide 2. Homologation to a monocarboxylic acid methyl ester malonate followed by deprotection and cyclization gave the macrocyclic frame. Further manipulation gave the desired compounds. Unlike the ortho-substituted benzofused macrocyclic lactams described in the previous paper which are selective NEP inhibitors, the meta-substituted compounds are dual inhibitors of both NEP and ACE. The most potent member of this new series, compound 16a, inhibited both enzymes with an IC50 = 8 nM in NEP and 4 nM in ACE.
...
PMID:Meta-substituted benzofused macrocyclic lactams as zinc metalloprotease inhibitors. 904 41

The micronucleus test is widely used to assess in vivo clastogenicity because of its convenience, but it is not appropriate for some carcinogenic chemical classes. Halogenated compounds, for example, are inconsistent micronucleus inducers. We assessed the genotoxicity of 7 haloalkanes and haloalkenes carcinogenic to rodents in 7 mouse organs-stomach, liver, kidney, bladder, lung, brain, and bone marrow-using the alkaline single cell gel electrophoresis (SCG) assay. The carcinogens we studied were 1, 2-dibromo-3-chloropropane (DBCP), 1,3-dichloropropene (mixture of cis and trans) (DCP), 1,2-dibromoethane (EDB), 1,2-dichloroethane (EDC), vinyl bromide, dichloromethane, and carbon tetrachloride; only DBCP induces micronuclei in mouse bone marrow. Except for carbon tetrachloride, halocompounds studied are mutagenic to Salmonella typhimurium. Mice were sacrificed 3 or 24 h after carcinogen administration. DCP and EDC induced DNA damage in all of the organs studied. Vinyl bromide yielded DNA damage in all of the organs except for bone marrow. DBCP induced DNA damage in the stomach, liver, kidney, lung, and bone marrow; EDB in the stomach, liver, kidney, bladder, and lung; and dichloromethane in the liver and lung. Since no deaths, morbidity, clinical signs, organ pathology, or microscopic signs of necrosis were observed, the DNA damage was not attributable to cytotoxicity. On the other hand, the positive response in the liver induced by carbon tetrachloride, which was accompanied by necrosis, was considered to be a false positive response. We suggest that the alkaline SCG assay can be used in multiple organs to detect in vivo genotoxicity that is not expressed in bone marrow cells in mice given non-necrogenic doses of halocompounds.
...
PMID:Detection of in vivo genotoxicity of haloalkanes and haloalkenes carcinogenic to rodents by the alkaline single cell gel electrophoresis (comet) assay in multiple mouse organs. 980 71

Liposomes encapuslating positron emitters are applicable for diagnostic imaging and are useful to investigate the real-time liposomal trafficking in vivo. Long-circulating liposomes encapsulaing [2-(18)F]-2-fluoro-2-deoxyglucose were administrated to tumor-bearing mice, and a PET scan was performed. Small-sized long-circulating liposomes (100 nm) tended to accumulate in tumor tissues of tumor-bearing mice as compared with conventional liposomes. Then the size effect on trafficking of long-circulating liposomes was investigated. Large-sized liposomes (>300 nm) accumulated in liver and spleen in a time dependent manner. On the contrary, small-sized ones (<200 nm) were transiently accumulated in the liver right after injection, but the accumulation decreased time dependently, suggesting that, although the majority of small long-circulating liposomes remain in bloodstream, some extravasate once into interstitial spaces in liver which re-enter into bloodstream again. Next the trafficking of so-called long-circulating liposomes, i.e., liposomes modified with ganglioside GM1, palmityl glucuronide (PGlcUA), and polyethylene glycol (PEG), in tumor-bearing mice was examined. The accumulation of all three kinds of long-circulating liposomes in liver decreased time-dependently, and PGlcUA-liposomes could avoid liver-trapping the most efficiently. Tumor accumulation of liposomes was obvious for PGlcUA-liposomes and PEG-liposomes from immediately after injection, but not for GM1-liposomes. Finally, the trafficking of differently charged liposomes was investigated in normal mice. The accumulation of positively charged liposomes containing 1,2-dimyristyloxypropyl-3-dimethyl-hydroxyethyl bromide was different from that of neutral and negatively charged DCP-liposomes. The agglutinability of and serum protein ginding to positively charged liposomes were marked, suggesting that these factors affect the high accumulation of DMRIE-liposomes in liver. Non-invasive PET analysis of liposomal trafficking is beneficial for obtaining information about liposomal drug delivery, and long-circulating liposomes might be useful for diagnostic tumor imaging by PET.
...
PMID:Delivery of contrast agents for positron emission tomography imaging by liposomes. 1083 26

Multiplex polymerase chain reaction (PCR) allows for the simultaneous amplification of several genes, thereby optimizing the use of reagents and decreasing personnel time. Multiplex PCR was used to amplify four genes in one PCR reaction, demonstrating the advantage of multiplex PCR for our study since it allowed us to amplify four separate genes using only 1 microl DNA, thus maximizing the use of study DNA. As compared with conventional multiplex PCR analysis with ethidium bromide, incorporating fluorescence-labeled primers into multiplex PCR reactions facilitated accurate, simultaneous analysis of many DNA fragments within one base discrimination. We have used this fluorescence methodology to analyze polymorphisms associated with either impaired fibrinolysis or myocardial infarction. These include the angiotensin converting enzyme insertion/deletion (I/D) polymorphism in intron 16 of the DCP1 gene, the Alu I/D polymorphism of the tissue plasminogen activator-25 locus in intron 8, the plasminogen activator inhibitor 4G/5G repeat polymorphism, and the variable number tandem repeat of the endothelial cell nitric oxide synthase gene, all characterized by an insertion, deletion, or repeat. The amplified products were diluted 1 : 60 and analyzed on the ABI PRISM 310 Genetic Analyzer using GeneScan software. With this method, we were able to amplify four genes using 75% less reagents and personnel time, thus demonstrating the benefit of multiplex PCR and fluorescence technology.
...
PMID:Fluorescent multiplex polymerase chain reaction analysis of four genes associated with inpaired fibrinolysis and myocardial infarction. 1146 7

Organosilicate nanocomposite hexagonal mesostructure (NHMS) was synthesized from dodecylamine and tetraethyl orthosilicate (TEOS). The nanocomposite (NMCM) of numbers 41, 48, and 50 were synthesized from cetyltrimethylammonium bromide (CTABr) and (TEOS). The rates, affinity, and stability of these synthetic nanocomposite materials to remove and retain chlorinated phenols from aqueous solution were investigated; all materials have the ability for sorption and retention of 2,4-dichlophenol (2,4-DCP). Batch absorption kinetics indicates that NHMS, NMCM-41, NMCM-48, and NMCM-50 are 1st order reactions, with rate constants of 0.412, 0.296, 0.112, and 0.0161 hr(-1), respectively. Average percent 2,4-DCP removal for NHMS, NMCM-41, NMCM-48, and NMCM-50 was 92, 98, 90, and 52%, respectively. Isothermic measurements fit Freundlich and Langmuir models. NHMS and NMCM-41 best fit Langmuir model. Stability of the adsorbents in 0.10 M CaCl2 for 56 days was in the order: NMCM-41 > NHMS > NMCM-50 > NMCM-48.
...
PMID:Organo-silicate nanocomposites for the removal of chlorinated phenols from aqueous media: kinetics and environmental stability. 1553 9

Prolonged hyperglycemia, dyslipidemia and oxidative stress in diabetes result in the production and accumulation of AGEs. It is now clear that AGEs contribute to the development and progression of cardiovascular disease in diabetes, as well as other complications. AGEs are thought to act through receptor-independent and dependent mechanisms to promote vascular damage, fibrosis and inflammation associated with accelerated atherogenesis. As a result, novel therapeutic agents to reduce the accumulation of AGEs in diabetes have gained interest as potential cardioprotective approaches. A variety of agents have been developed which are examined in detail in this review. These include aminoguanidine, ALT-946, pyridoxamine, benfotiamine, OPB-9195, alagebrium chloride, N-phenacylthiazolium bromide and LR-90. In addition, it has been demonstrated that a number of established therapies have the ability to reduce the accumulation of AGEs in diabetes including ACE inhibitors, angiotensin receptor antagonists, metformin, peroxisome proliferators receptor agonists, metal chelators and some antioxidants. The fact that many of these inhibitors of AGEs are effective in experimental models, despite their disparate mechanisms of action, supports the keystone role of AGEs in diabetic vascular damage. Nonetheless, the clinical utility of AGE inhibition remains to be firmly established. Optimal metabolic and blood pressure control, that is achieved early and sustained indefinitely, remains the best recourse for inhibition of AGEs until more specific interventions become a clinical reality.
...
PMID:The role of AGEs and AGE inhibitors in diabetic cardiovascular disease. 1602 65

In this study, the interaction of the anion of quinapril (QUIN), angiotensin converting enzyme (ACE) inhibitor, with cationic surfactant cetyltrimethylammonium bromide (CTAB) was investigated. The effect of cationic micelles on the spectroscopic and acid-base properties of QUIN was studied at pH 8. The binding of QUIN anion to CTAB micelles implied a shift in drug acidity constant (pK(a)(water)-pK(a)(micelle)=1.39) proving the great affinity of negatively charged QUIN ion for the positively charged CTAB micelle surface. The strong dependence of the partition coefficient K(x) on QUIN concentration, obtained by using pseudo-phase model, is consistent with an adsorption-like phenomenon. From the dependence of differential absorbance at lambda=272 nm on CTAB concentration, by using mathematical model that treats the solubilization of QUIN anion as its binding to specific sites in the micelles (Langmuir adsorption isotherm), the binding constant K(b)=(2.3+/-0.4)x10(3) mol(-1)dm(3) was obtained. QUIN-CTAB binding constant was also calculated from micellar liquid chromatography (MLC) and this method was found to be not accurate enough for its determination.
...
PMID:Interaction of quinapril anion with cationic surfactant micelles of cetyltrimethylammonium bromide. 1676 77

Effects of contact time, monochloramine doses, monochloramine application modes, pH, temperature and bromide ion concentrations on formation of disinfection by-products (DBPs), including haloacetonitriles, haloketones, chloropicrin, cyanogen halides and trihalomethanes, during chloramination were investigated using model solutions containing 5 mg/L (as DOC) Suwannee River natural organic matter (NOM). Chloramine speciation and some DBPs were measured using membrane introduction mass Spectrometer (MIMS). Longer reaction times led to continued formation over time for dichloroacetonitrile (DCAN), 1,1-dichloro-2-propanone (1,1-DCP) and chloroform. Cyanogen chloride (CNCl) formation occurred over time, but after reaching a peak concentration CNCl concentrations decreased over longer time periods. Linear relationships were observed between the formation of DCAN, 1,1-DCP, CNCl or chloroform and the dosage of monochloramine. Chloramination modes (addition of preformed monochloramine or variable sequential additions of free chlorine and ammonium salts) exhibited the largest impact on chloroform formation but displayed little effect on the formation of DCAN, 1,1-DCP and CNCl. Over the range in pH from 4 to 9 profound differences in DBP formation were observed; pH values between 5 and 6 resulted in the highest DBP concentrations. An increase in temperature enhanced the formation of chloroform but did not affect DCAN, 1,1-DCP and CNCl formation. Chloropicrin concentrations were always low (around detection limits) under all conditions. Increasing the concentrations of bromide ions enhanced the formation of bromine-substituted DBPs.
...
PMID:Factors affecting formation of haloacetonitriles, haloketones, chloropicrin and cyanogen halides during chloramination. 1727 Feb 34

Mixed hemimicelles solid-phase extraction (SPE) based on cetyltrimethylammonium bromide (CTAB)-coated nano-magnets Fe3O4 was investigated for the preconcentration of four chlorophenols (CPs) in environmental water samples prior to HPLC-spectrophotometry determination in this paper. By the rapid isolating (about 5 min) of Fe3O4 nanoparticles (NPs) through placing a Nd-Fe-B strong magnet on the bottom of beaker, the time-consuming preconcentration process of loading large volume sample in conversional SPE method with a column can be avoided. The unique properties of Fe3O4 NPs such as high surface area and strong magnetism were utilized adequately in the SPE process. This novel separation method produced a high preconcentration rate and factor. A comprehensive study of the adsorption conditions such as the Fe3O4 NPs zeta-potential, CTAB added amounts, pH value, standing time and maximal extraction volume was also presented. Under optimized conditions, four analytes of 2-chlorophenol (2-CP), 2,4-dichlorophenol (2,4-DCP), 2,4,6-trichlorophenol (TCP) and pentachlorophenol (PCP) were quantitatively extracted. The method was then used to determine four CPs in five real environmental water samples. High concentration factors (700) were achieved for each of the analytes, with observed detection limits ranging between 0.11 and 0.15 microg L(-1). The accuracy of method was evaluated by recovery measurements on spiked samples. Good recovery results (83-98%) with satisfactory relative standard deviation (RSD) were achieved. It is important to note that satisfactory preconcentration factors and extraction recoveries for the four CPs were obtained with only a little amount of Fe3O4 NPs (0.1g) and CTAB (60 mg). To the best of our knowledge, this was the first time a mixed hemimicelles SPE method based on Fe3O4 NPs magnetic separation had been used for the pretreatment of environmental water samples.
...
PMID:Mixed hemimicelles solid-phase extraction based on cetyltrimethylammonium bromide-coated nano-magnets Fe3O4 for the determination of chlorophenols in environmental water samples coupled with liquid chromatography/spectrophotometry detection. 1817 1


<< Previous 1 2 3 4 Next >>

---