Disease relevance of dihydroxy-oxo-phosphanium

• A phosphonate monoester, m-carboxyphenyl phenylacetamidomethylphosphonate, has been found to be a specific inhibitor of the class C beta-lactamase of Enterobacter cloacae P99 [1].
• The problems of nonhematopoietic toxicity from whole-body irradiation might be circumvented by using a bone-seeking radiopharmaceutical, such as samarium-153 ethylenediaminetetramethylene phosphonate (153Sm-EDTMP), to ablate the bone marrow [2].
• A hydrolytic catalytic antibody, generated against a nitrophenyl phosphonate transition state analogue, has been cloned and expressed in Escherichia coli for use as a model system to demonstrate the feasibility of using genetic selections to enhance catalytic activity [3].
• HIV inhibitory activity was found to be dependent on both chain length and the number of phosphonate residues [4].
• A phase I study of samarium-153 ethylenediaminetetramethylene phosphonate therapy for disseminated skeletal metastases [5].

Psychiatry related information on dihydroxy-oxo-phosphanium

• This method of monolayer formation contrasts the requirement for heating and long reaction times found to be necessary to form phosphonate monolayers on other metal oxide substrates, such as titanium and silicon [6].

High impact information on dihydroxy-oxo-phosphanium

• Using the hippocampal slice preparation, we now report that the phosphonic acid derivative of baclofen, phaclofen, is a remarkably selective antagonist of both the postsynaptic action of baclofen and the bicuculline-resistant action of GABA, and that it selectively abolishes the slow inhibitory postsynaptic potential in pyramidal cells [7].
• The x-ray structures of three esterase-like catalytic antibodies identified by screening for catalytic activity the entire hybridoma repertoire, elicited in response to a phosphonate transition state analog (TSA) hapten, were analyzed [8].
• The three-dimensional structure of an unusually active hydrolytic antibody with a phosphonate transition state analog (hapten) bound to the active site has been solved to 2.5 A resolution [9].
• Immunization with a phosphonate monoester transition-state analog of cocaine provided monoclonal antibodies capable of catalyzing the hydrolysis of the cocaine benzoyl ester group [10].
• An antibody generated against a neutral phosphonate diester transition-state analog was found to catalyze the aminoacylation of the 3'-hydroxyl group of thymidine with an alanyl ester [11].

Chemical compound and disease context of dihydroxy-oxo-phosphanium

• The acyclic nucleoside phosphonate analogue cidofovir elicited a marked protection against hemangioma growth in newborn rats that had been infected i.p. with a high titer of murine polyomavirus [12].
• Experiments were performed to evaluate the ability of the enzymes of Escherichia coli involved in glycerol 3-phosphate metabolism to recognize phosphonic acid analogues of the natural substrate [13].
• A phosphonate monoesterase gene (pehA) encoding an enzyme that hydrolyzes phosphonate esters including glyceryl glyphosate to glyphosate and glycerol was cloned from the glyphosate metabolizing bacterium, Burkholderia caryophilli PG2982 [14].
• Towards this end, antibodies capable of binding and hydrolyzing cocaine were identified by phage display from a biased single chain antibody library generated from the spleens of mice previously immunized with a cocaine phosphonate transition state analog hapten [15].
• Chemical modifications in the molecule of parental ANP aimed at blocking of phosphonate charges resulted in a set of promising derivatives, two of which have been recently approved for treatment of hepatits B (Hepsera((R))) and HIV (Viread((R))) [16].

Biological context of dihydroxy-oxo-phosphanium

• The IC50 for the amide was 4.4 x 10(-4) mol fraction and for the phosphonate was 1.6 x 10(-5) mol fraction [17].
• This work shows that these ligands exhibit excellent enantioselectivity in rhodium-catalyzed asymmetric hydrogenation of alpha,beta-unsaturated phosphonic acid derivatives [18].
• Other recognizable gene clusters include many involved in catabolic activities such as protocatechuate utilization and phosphonate degradation [19].
• A keto analog of PALA, 4,5-dicarboxy-2-ketopentyl phosphonate, also binds tightly to the catalytic subunit and induces a very similar conformational change, whereas an alcohol analog, 4,5-dicarboxy-2-hydroxypentyl phosphonate, does not bind tightly, indicating the critical importance of an unhindered carbonyl group with trigonal geometry [20].
• The kinetics of binding and dissociation of stable phosphonate analogs of the tetrahedral intermediate (Alberg, D., and Bartlett, P.A. (1989) J. Am. Chem. Soc. 111, 2337) were also examined [21].

Anatomical context of dihydroxy-oxo-phosphanium

• The crystal structure of human neutrophil cathepsin G, complexed with the peptidyl phosphonate inhibitor Suc-Val-Pro-PheP-(OPh)2, has been determined to a resolution of 1.8 A using Patterson search techniques [22].
• One such novel phosphonate quinoxalinedione derivative and competitive AMPA antagonist ZK200775 exhibited a surprisingly long therapeutic time window of >4 h after permanent occlusion of the middle cerebral artery in rats and was devoid of renal toxicity [23].
• Most of the nucleophilic reactivity of B cells measured by formation of covalent adducts of a hapten amidino phosphonate diester was attributed to micro and kappa/lambda subunits of the B cell receptor [24].
• The majority of CD4(+) T cells repopulating the intestinal mucosa following PMPA therapy were CD29(hi) and CD11ahi [25].
• Phosphonate 9-[2-(phosphomethoxypropyl]adenine (PMPA) treatment led to a moderate suppression of intestinal viral loads and repopulation of intestinal mucosa by predominantly activated memory CD4(+) T-helper cells [25].

Associations of dihydroxy-oxo-phosphanium with other chemical compounds

• An antibody generated against a neutral phosphonate diester transition-state (TS not equal to) analog catalyzes the formation of an amide bond between a phenylalanyl amino group and an acyl azide derived from L-alanine [26].
• Antibodies elicited against a phosphonate transition-state analogue were found to catalyze hydrolysis of a nonbioactive chloramphenicol monoester as a prodrug at a significantly higher rate above the uncatalyzed background reaction to regenerate chloramphenicol as a parent molecule [27].
• Inhibition of fibroblast growth factor-2-induced vascular tumor formation by the acyclic nucleoside phosphonate cidofovir [28].
• The phosphonate compound 2-aminoethylphosphonate is present as a component of complex carbohydrates on the surface membrane of many trypanosomatids including glycosylinositolphospholipids of Trypanosoma cruzi [29].
• The finding that phosphonate modification at each of the 536 and 564 sites can promote interaction with the Grb2 adaptor protein indicates that the intramolecular interactions fostered by post-translational modifications of tyrosine are not energetically strong and susceptible to intermolecular competition [30].

Gene context of dihydroxy-oxo-phosphanium

• (S, S)-3-Cyclohexyl-2-[[5-(2, 4-difluorophenyl)-2-[(phosphonomethyl)amino]pent-4-ynoyl]amino] propio nic acid (47), an arylacetylene amino phosphonate dipeptide, was found to inhibit ECE-1 and NEP with IC50 values of 14 nM and 2 microM, respectively [31].
• The selectivity of CYP2C8 in catalyzing phosphonate O-deethylation indicates that coadministration of drugs that are metabolized by the same enzyme requires careful consideration [32].
• Thus, the phosphonate moiety in this analog represents an important new lead in the development of FPGS inhibitors [33].
• On the basis of mutational analysis, the genes for phosphonate uptake and degradation in Escherichia coli were shown to be organized in a 10.9-kb operon of 14 genes (named phnC to phnP) and induced by phosphate (P(i)) starvation [Metcalf and Wanner (1993) J Bacteriol 175: 3430-3442] [34].
• 3-(3-Actamide-1-benzyl-2-ethylindolyl-5-oxy)propane phosphonic acid (LY311727), a potent inhibitor of human group IIA PLA2, strongly inhibits GV-PLA2 with an IC50 value of about 36 nM which is comparable to its inhibition of group IIA PLA2 [35].

Analytical, diagnostic and therapeutic context of dihydroxy-oxo-phosphanium

• 166Holmium ethylenediaminetetramethylene phosphonic acid (166Ho-EDTMP) is a short-lived beta-emitting radionuclide complexed to an aminophosphonate ligand that we have investigated in a canine model as a potential agent for specific marrow ablation before marrow transplantation [36].
• The produced protected oligomers were treated with thiophenol and triethylamine to remove the phosphonate protecting groups, cleaved from the solid support using concentrated aqueous ammonia, and purified by HPLC [37].
• Because of the phosphonate linkage each dinucleotide exists as a diastereomeric pair as shown by thin layer chromatography and enzymatic studies [38].
• New approach to oligonucleotide microarrays using zirconium phosphonate-modified surfaces [39].
• It is concluded that these phosphonate-enzyme interactions evidenced by both (31)P solution NMR and X-ray are too weak to be preserved under the lyophilization of KDO8PS-2 binary complex and therefore are not evidenced by the solid-state REDOR spectra [40].

References