Anti-Phos

These assays are based upon the use of a europium or terbium chelate (a transition metal-ligand complex displaying long-lived fluorescent properties) and labeled anti-phosphopeptide or anti-phos-photyrosine antibodies that can bind to phosphorylated peptides. The antibodies are usually labeled... 

Anti-Phos Ab array BCG mycobacterium infection of host Monocyte THP-1 cells Activation of SAP kinase cJun, i PKC vare T a-adducin, GSK-3 3 by BCG infection... 

The 4-thiazolidinyl phosphonates 143 (Scheme 44) are known for their therapeutical properties, in particular as anti-inflammatory agents [5,89]. Their asymmetric synthesis by hydrophosphonylation of 3-thiazolines has been described using various chiral auxiliaries chiral phosphites such as (2S,4i )-2H-2-oxo-5,5-dimethyl-4-phenyl-l,3,2-dioxaphosphorinane (de = 2-8%) [90] or BINOL-phos-phite (de = 65-90%) [91] and also chiral catalyst such as titanium or lanthanide chiral complexes (ee = 29-98%) [92]. Hydrophosphonylation of C2-chiral3-thi-azolines has also been performed (de = 32-38%) [93]. 

Filamentous tau is hyperphosphorylated. This is an early event that appears to precede filament assembly. It also renders tau unable to interact with microtubules. Much effort has gone into the mapping of phosphorylation sites and the identification of candidate protein kinases and phosphatases. For sites that are also phos-phorylated in normal brain tau, a higher proportion of tau molecules is phosphorylated in filamentous tau. In addition, filamentous tau is phosphorylated at more serine and threonine residues than tau from normal adult brain. Phosphorylation-dependent anti-tau antibodies were instrumental for the study of many phosphorylation sites. In particular, phosphorylation of S214 and S422 was found to be specific for assembled tau. 

With a BINAP-Ru [3d,104], Hg-BINAP-Ru [102], or P-Phos-Ru [25] catalyst, the anti-inflammatory drugs (S)-ibuprofen and (S)-naproxen could be efficiently synthesized via enantioselective hydrogenation (Scheme 26.9). In these cases, high hydrogenation pressure and low temperature are required to achieve good enantioselectivity. With an (R)-BIPHEMP-Ru catalyst, (S)-2-(4-fluorophenyl)-3-methylbutanoic acid, a key intermediate for the synthesis of the calcium antago-... 

The ester must in addition contain some group which will initiate the approach of the ester to the surface of the enzyme. In this connexion it should be noted that di-isopropyl phos-phorochloridate (III, X = Cl), in which the chlorine atom is chemically very reactive,3 has no toxic properties, is devoid of myotic and anti-cholinesterase activity. In this compound, the chlorine is hydrolysed very quickly in water and would probably be destroyed extremely quickly in vivo. We have shown, quite conclusively, that in non-polar solvents the phosphorochloridate... 

Liposome-encapsulated immunomodulators are currently under investigation in different patient groups although this development has certainly not advanced as far as that with the liposomal anthracyclines. MLV-MTP-PE (multilamellar vesicles-muramyl tripeptide-phos-phatidylethanolamine) was studied in several clinical trials in osteosarcoma patients who developed pulmonary metastases during adjuvant chemotherapy [108], The intravenous administration of MLV-MTP-PE induced tumouricidal properties in monocytes as well as increase in serum IL-1 shortly after intravenous infusion. Furthermore elevations in C-reactive protein, 32-microglobulin and ceruloplasmin were frequently observed. Even higher anti-tumour activity was observed in combination with ifosfamide. These preliminary results suggests that liposome-encapsulated immunomodulators in combination with chemotherapy may be an appropriate treatment for recurrent disease. 

S Lin, I Hsiao, SM Hsu. Determination of the dissociation constant of phos-vitin-anti-phosphoserine interaction by affinity capillary electrophoresis. Anal Biochem 254 9-17, 1997. 

Calcium Acetate (PhosLo) [Calcium Supplement/ Anti arrhythmic/Mmeral/ Electrolyte] Uses ESRD-associated hyper-phos-phatemia Action Ca " supl w/o aluminum to X P04 absorption Dose 2-4 tabs PO w/ meals Caution [C, ] Contra t Ca Disp Gelcap SE Can t Ca, hypophosphatemia, constipation Interactions t Effects OF quinidine X effects W/ large intake of dietary fiber, spinach, rhubarb X effects OF atenolol, CCB, etidronate, tetracyclines, fluoroquinolones, phenytoin, Fe salts, thyroid hormones EMS Pts have reduced renal Fxn, monitor ECG for signs of electrolyte disturbances OD S/Sxs of hypercalcemia (confusion, weakness, GI upset, constipation, N, V, and cardiac arrhythmias) give IV fluid for diuresis symptomatic and supportive Calcium Carbonate (TumS/ Alka Mints) [Antacid/ Calcium Supplement/Mineral/ Electrolyte] [OTC] Uses Hyperacidity associated w/ peptic ulcer Dz, hiatal hernia, etc Action Neutralizes gastric acid Dose 500 mg—2 g PO PRN -1- in renal impair Caution [C, ] Disp Chew tabs, susp SE t -1- PO constipation Interactions X Effect OF tetracyclines, fluo-... 

Dichloro(trifluorovinyl)phosphane and chlorobis(trifluorovinyl)phosphane react with anti-mony(V) fluoride at room temperature undergoing not only substitution of chlorine but also addition of two fluorine atoms to the phosphorus to give tetrafluoro(trifluorovinyl)-A5-phos-phane and trifluorobis(trifluorovinyl)-A5-phosphane, respectively.100... 

Trialkylphosphines add via anti addition to give the expected salts (577 Scheme 81) which decompose upon work-up to products (578) not containing phosphorus.145 Triethyl phosphite (equation 132) reacts with propiolic acid (572) or methyl propiolate (506) to give predominately (>90%) the P-phos-phono ester (579) with the ( -configuration.l4Sb... 

The differences in membrane behavior of active and inactive anti-inflammatory drugs became visible in their effects on bacteriorhodopsin incorporated into phos-... 

The most efficient catalyst precursors were found in the RuCl2(arene)(phos-phine) series. These complexes are known to produce ruthenium vinylidene species upon reaction with terminal alkynes under stoichiometric conditions, and thus are able to generate potential catalysts active for anti-Markovnikov addition [8]. Dienylcarbamates could also be selectively prepared from conju-... 

The active nickel catalyst contains one bidentate phos-phinite ligand and the overall mechanism of the reaction is believed to be similar to butadiene hydrocyanation except that the final reductive elimination step is irreversible under the conditions of the reaction. jr-Allyl intermediates (7) are believed to play an important role in the exclusive formation of the branched nitrile product observed. Formation of the C-CN bond in the final reductive ehmination from the r-allyl intermediate occurs at C(2) and not C(4), because the aromaticity of the naphthalene ring is preserved only when the bond forms with C(2). A a-alkyl complex see a-Bond) with the Ni bound to C(l), which could give the linear (anti-Markovnikov) nitrile product, does not contribute because of the much greater stability of intermediate (7), accounting for the high regioselectivity observed. 

Fidder, A., Hulst, A.G., Noort, D., De Ruiter, R., Van der Schans, M.J., Benschop, H.P., Langenberg, J.P. (2002). Retrospective detection of exposure to organophosphorous anti-cholinesterases mass spectrometric analysis of phos-phylated human butyrylcholinesterase. Chem. Res. Toxicol. 15 582-90. ... 

Moore E, Chappuis PP. A comparative study of the photochemistry of the nonsteroidal anti-inflammatory drugs, naproxen, benoxaprofen and indomethacin. Photochem Pho-tobiol 1988 47 173-180. 

Statins are well absorbed after administration orally, and are metabolised in the liver. They are well tolerated, the commonest adverse effect being transient, and usually minor abnormality of liver function tests in some 1% of patients. Asymptomatic elevation of muscle enzymes (creatine phos-phokinase, CPK) and myositis (with a generalised muscle discomfort) occur more rarely, but is more frequent when statins are combined with other anti-hyperlidaemic drugs such as fibrates and nicotinic acid patients should be counseled about myositis when these drugs are co-administered. Myositis is also more likely with co-administered anti-HIV protease inhibitors, and with drugs that interfere with metabolism of some statins, e.g. ciclosporin. 

The observed activation of allyltrihalosilanes with fluoride ion and DMF and the proposition that these agents are bound to the silicon in the stereochemistry-determining transition structures clearly suggested the use of chiral Lewis bases for asymmetric catalysis. The use of chiral Lewis bases as promoters for the asymmetric allylation and 2-butenylation of aldehydes was first demonstrated by Denmark in 1994 (Scheme 10-31) [55]. In these reactions, the use of a chiral phos-phoramide promoter 74 provides the homoallylic alcohols in high yield, albeit modest enantioselectivity. For example, the ( )-71 and benzaldehyde affords the anti homoallylic alcohol 75 (98/2 antUsyn) in 66% ee. The sense of relative stereoinduction clearly supports the intermediacy of a hexacoordinate silicon species. The stereochemical outcome at the hydroxy center is also consistent with a cyclic transition structure. 

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