Metal-Based PSMA Radioligands.

Prostate cancer is one of the most common malignancies for which great progress has been made in identifying appropriate molecular targets that would enable efficient in vivo targeting for imaging and therapy. The type II integral membrane protein, prostate specific membrane antigen (PSMA) is overexpressed on prostate cancer cells in proportion to the stage and grade of the tumor progression, especially in androgen-independent, advanced and metastatic disease, rendering it a promising diagnostic and/or therapeutic target. From the perspective of nuclear medicine, PSMA-based radioligands may significantly impact the management of patients who suffer from prostate cancer. For that purpose, chelating-based PSMA-specific ligands have been labeled with various diagnostic and/or therapeutic radiometals for single-photon-emission tomography (SPECT), positron-emission-tomography (PET), radionuclide targeted therapy as well as intraoperative applications. This review focuses on the development and further applications of metal-based PSMA radioligands.

Degradation of acephate by Enterobacter asburiae, Bacillus cereus and Pantoea agglomerans isolated from diamondback moth Plutella xylostella (L), a pest of cruciferous crops.

Acephate-degrading bacterial isolates were isolated from the larval gut of diamondback moth Plutella xylostella, a notorious pest of cruciferous crops worldwide that has developed resistance to insecticides. Partial 16S rRNA gene sequencing identified the isolates as Bacillus cereus (PX-B.C.Or), Enterobacter asburiae (PXE), and Pantoae agglomerans (PX-Pt.ag.Jor). All isolates grew on minimal media (MM) in the presence of acephate at 100 and 200 ppm, with maximum growth at 200 ppm. LC-MS analyses of spent medium showed that E. asburiae degraded acephate to methamidophos and O, O-dimethyl phosporamidate and B. cereus O,S-dimethyl to phosphorothioate but P. agglomerans to an unnamed compound. All three isolates used acephate as a source of carbon and energy for growth; however, P. agglomerans used it also as source of sulphur. Strong evidence revealed that the bacterial communities present in the gut of diamondback moth might aid in acephate degradation and play a role in the development of insecticide resistance.

Bio-remediation of acephate-Pb(II) compound contaminants by Bacillus subtilis FZUL-33.

Removal of Pb(2+) and biodegradation of organophosphorus have been both widely investigated respectively. However, bio-remediation of both Pb(2+) and organophosphorus still remains largely unexplored. Bacillus subtilis FZUL-33, which was isolated from the sediment of a lake, possesses the capability for both biomineralization of Pb(2+) and biodegradation of acephate. In the present study, both Pb(2+) and acephate were simultaneously removed via biodegradation and biomineralization in aqueous solutions. Batch experiments were conducted to study the influence of pH, interaction time and Pb(2+) concentration on the process of removal of Pb(2+). At the temperature of 25°C, the maximum removal of Pb(2+) by B.subtilis FZUL-33 was 381.31±11.46mg/g under the conditions of pH5.5, initial Pb(2+) concentration of 1300mg/L, and contact time of 10min. Batch experiments were conducted to study the influence of acephate on removal of Pb(2+) and the influence of Pb(2+) on biodegradation of acephate by B.subtilis FZUL-33. In the mixed system of acephate-Pb(2+), the results show that biodegradation of acephate by B.subtilis FZUL-33 released PO4(3+), which promotes mineralization of Pb(2+). The process of biodegradation of acephate was affected slightly when the concentration of Pb(2+) was below 100mg/L. Based on the results, it can be inferred that the B.subtilis FZUL-33 plays a significant role in bio-remediation of organophosphorus-heavy metal compound contamination.

Photocatalytic degradation of acephate in pak choi, Brassica chinensis, with Ce-doped TiO2.

The photocatalytic degradation of acephate was investigated using Ce-doped TiO2 (TiO2/Ce) hydrosol. In contrast to previous research conducted under artificial light in the laboratory, this study investigated the decomposition of acephate in a field trial. The results show that acephate can be efficiently degraded by the TiO2/Ce system under natural field conditions; the degradation efficiency was affected by the dosage of the photocatalyst and acephate. The optimum dosage of TiO2/Ce was 2400 g a.i.ha(-1), and the photodegradation efficiency of acephate reached 93.5% after 20 h at an acephate dosage of 675 g a.i.ha(-1). Ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) analysis detected and identified four degradation products-methamidophos, phosphorothioic acid O,O,S-trimethyl ester, S-methyl methanethiosulfonate and phosphorous acid-that were formed during the TiO2/Ce photodegradation of acephate. Based on the structural identification of the degradation products, a probable photodegradation pathway was proposed, and the first decomposition step may be the cleavage of the C‒N bond of acephate. Subsequently, the P‒S and P‒O bonds may be oxidized gradually or simultaneously to complete the mineralization.

Key amino acid associated with acephate detoxification by Cydia pomonella carboxylesterase based on molecular dynamics with alanine scanning and site-directed mutagenesis.

Insecticide-detoxifying carboxylesterase (CE) gene CpCE-1 was cloned from Cydia pomonella. Molecular dynamics (MD) simulation and computational alanine scanning (CAS) indicate that Asn 232 in CpCE-1 constitutes an approximate binding hot-spot with a binding free energy difference (ΔΔGbind) value of 3.66 kcal/mol. The catalytic efficiency (kcat/km) of N232A declined dramatically, and the half inhibitory concentrations (IC50) value increased by more than 230-fold. Metabolism assay in vitro reveals that the acephate could be metabolized by wild CpCE-1, whereas N232A mutation is unable to metabolize the acephate, which suggests that the hot-spot Asn 232 is a crucial residue for acephate metabolism. Mutation detection suggests that low frequency of Asn 232 replacement occurred in Europe field strains. Our MD, CAS, site-directed mutagenesis, and metabolism studies introduce a new amino acid residue Asn 232 involved in the metabolism of the acephate with CpCE-1, and this method is reliable in insecticide resistance mechanism research and prediction of key amino acids in a protein which is associated with specific physiological and biochemical functions.

Biodegradation of acephate and methamidophos by a soil bacterium Pseudomonas aeruginosa strain Is-6.

The aim of this study was to isolate and characterize a new acephate-degrading bacteria from agricultural soil and to investigate its biodegradation ability and pathway of degradation. A bacterial strain Is-6, isolated from agriculture soil could completely degrade and utilize acephate as the sole carbon, phosphorus and energy sources for growth in M9 medium. Analysis of the 16S rRNA gene sequence and phenotypic analysis suggested that the strain Is-6 was belonging to the genus Pseudomonas aeruginosa. Strain Is-6 could completely degrade acephate (50 mg L(-1)) and its metabolites within 96 h were identified by high-performance liquid chromatography (HPLC) and electron spray ionization-mass spectrometry (ESI-MS) analyses. When exposed to the higher concentration, the strain Is-6 showed 92% degradation of acephate (1000 mg L(-1)) within 7 days of incubation. It could also utilize dimethoate, parathion, methyl parathion, chlorpyrifos and malathion. The inoculation of strain Is-6 (10(7) cells g(-1)) to acephate (50 mg Kg(-1))-treated soil resulted in higher degradation rate than in noninoculated soils. These results highlight the potential of this bacterium to be used in the cleanup of contaminated pesticide waste in the environment.

Environmental behavior of the chiral organophosphorus insecticide acephate and its chiral metabolite methamidophos: enantioselective transformation and degradation in soils.

Acephate is a widely used organophosphorus insecticide globally, although there are some concerns about its usage with regard to acute consumer exposure and side-effects on nontarget organisms. These concerns are always attributed to the acephate metabolite methamidophos. In the many reports about the environmental behavior of acephate and its metabolite, none pay any attention to the chirality of them. In this study, the enantiomeric transformation and degradation of acephate was investigated in three soils under laboratory conditions using enantioselective GC-MS/MS. Racemic and enantiopure compounds were incubated in separate experiments. The degradation of racemates was shown to be enantioselective in unsterilized soils but not in the sterilized soils, thus confirming the enantioselectivity was microbially based. The priority of enantiomer degradation and transformation varied among soils and racemates. R-(+)-methamidophos was enriched in the Zhengzhou soil, but degraded faster in the Changchun and Nanchang soils than its antipode. For acephate, the Nanchang soil enriched R-(+)-acephate, and S-(-)-acephate accumulated in the other two soils. Acephate and methamidophos were both configurationally stable in soil, showing no interconversion of R-(+)- to S-(-)-enantiomers, or vice versa. The conversion of acephate to methamidophos proceeded with retention of configuration. Generally, the degradation followed approximate first-order kinetics, but showed significant lag phases.

Expression and subcellular localization of organophosphate hydrolase in acephate-degrading Pseudomonas sp. strain Ind01 and its use as a potential biocatalyst for elimination of organophosphate insecticides.

UNLABELLED: Organophosphate hydrolase (OPH), the product of an organophosphate-degrading (opd) gene cloned from Brevundimonas diminuta, hydrolyses the triester linkage found in neurotoxic organophosphate (OP) insecticides and nerve agents. Despite the fact that OPHs have a broad substrate range, OP compounds with a P-S linkage, such as insecticides like acephate, are poor substrates for the enzyme. Expression of OPH in acephate-utilizing Pseudomonas sp. Ind01 generated a live biocatalyst capable of degrading a wide range of OP insecticides. The heterologously expressed OPH, which is a substrate of twin arginine transport (Tat) pathway, successfully targeted to the membrane of Pseudomonas sp. Ind01. The membrane-associated OPH had a size that coincided with the mature form of OPH (mOPH), suggesting successful processing and targeting of the expressed OPH to the membrane. Pseudomonas sp. Ind01 expressing OPH degraded a variety of OP insecticides besides using acephate as sole carbon source. SIGNIFICANCE AND IMPACT OF THE STUDY: A biocatalyst capable of degrading a wide range of organophosphate (OP) insecticides was generated by expressing an organophosphate degradation gene in Pseudomonas sp. Ind01 involved in mineralization of acephate. The biocatalyst can be used to eliminate a wide range of OP insecticide residues from the environment.

Kinetic Study of the Biodegradation of Acephate by Indigenous Soil Bacterial Isolates in the Presence of Humic Acid and Metal Ions.

Many bacteria have the potential to use specific pesticides as a source of carbon, phosphorous, nitrogen and sulphur. Acephate degradation by microbes is considered to be a safe and effective method. The overall aim of the present study was to identify acephate biodegrading microorganisms and to investigate the degradation rates of acephate under the stress of humic acid and most common metal ions Fe(III) and copper Cu(II). Pseudomonas azotoformanss strain ACP1, Pseudomonas aeruginosa strain ACP2, and Pseudomonas putida ACP3 were isolated from acephate contaminated soils. Acephate of concentration 100 ppm was incubated with separate strain inoculums and periodic samples were drawn for UV-visible, FTIR (Fourier-transform infrared spectroscopy) and MS (Mass Spectrometry) analysis. Methamidophos, S-methyl O-hydrogen phosphorothioamidate, phosphenothioic S-acid, and phosphenamide were the major metabolites formed during the degradation of acephate. The rate of degradation was applied using pseudo-first-order kinetics to calculate the half-life (t1/2) values, which were 14.33-16.72 d-1 (strain(s) + acephate), 18.81-21.50 d-1 (strain(s) + acephate + Cu(II)), 20.06 -23.15 d-1 (strain(s) + acephate + Fe(II)), and 15.05-17.70 d-1 (strains + acephate + HA). The biodegradation efficiency of the three bacterial strains can be ordered as P. aeruginosa > P. putida > P. azotoformans. The present study illustrated the decomposition mechanism of acephate under different conditions, and the same may be applied to the removal of other xenobiotic compounds.