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101.
Glaser M Morrison M Solbakken M Arukwe J Karlsen H Wiggen U Champion S Kindberg GM Cuthbertson A 《Bioconjugate chemistry》2008,19(4):951-957
Achieving high-yielding, robust, and reproducible chemistry is a prerequisite for the (18)F-labeling of peptides for quantitative receptor imaging using positron emission tomography (PET). In this study, we extend the toolbox of oxime chemistry to include the novel prosthetic groups [(18)F]-(2-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}ethoxy)acetaldehyde, [(18)F]5, and [(18)F]-4-(3-fluoropropoxy)benzaldehyde, [(18)F]9, in addition to the widely used 4-[(18)F]fluorobenzaldehyde, [(18)F]12. The three (18)F-aldehydes were conjugated to the same aminooxy-bearing RGD peptide and the effect of the prosthetic group on biodistribution and tumor uptake studied in mice. The peptide conjugate [(18)F]7 was found to possess superior in vivo pharmacokinetics with higher tumor to blood, tumor to liver, tumor to muscle, and tumor to lung ratios than either [(18)F]10 or [(18)F]13. The radioactivity from the [(18)F]7 conjugate excreted more extensively through the kidney route with 79%id passing through the urine and bladder at the 2 h time point compared to around 55%id for the more hydrophobic conjugates [(18)F]10 and [(18)F]13. The chemical nature of a prosthetic group can be employed to tailor the overall biodistribution profile of the radiotracer. In this example, the hydrophilic nature of the ethylene glycol containing prosthetic group [(18)F]5 clearly influences the overall excretion pattern for the RGD peptide conjugate. 相似文献
102.
OBJECTIVE: To review the clinical and cytomorphologic features of 14 chordomas diagnosed by fine needle aspiration biopsy (FNAB) at our institution. STUDY DESIGN: The cytology files from January 1985 to February 2000 at Mayo Clinic, Rochester, Minnesota, U.S.A., were searched for all cases diagnosed as chordoma by FNAB. Clinical, radiographic and cytomorphologic findings of each case were reviewed. RESULTS: Ten males and four females (mean age, 55 years; range, 14-78) had tumors involving the sacrum (8), clivus (3) and vertebrae (lumbar, 2; cervical, 1). Pain was the presenting symptom in 11 patients. Most smears (82%) were cellular with a fibrillary background. Chondroid matrix was recognized in nine cases. Small, epitheliallike cells constituted the predominant cellular component in nine cases. Cells with clear, vacuolated cytoplasm were seen in almost 'every case; however, true physaliferous cells were rare. Mitotic figures were seen in four cases, binucleation in six and multinucleated giant cells in seven. Needle biopsies contained diagnostic material in all cases. Of the nine patients with follow-up (mean, 57 months; range, 3-184 months), three patients were alive and free of disease, five were alive with disease, and one was dead of disease at this writing. CONCLUSION: Because various cytologic presentations and overlapping cytologic features occur between chordoma, chondrosarcoma and metastatic clear cell carcinoma, it is important to recognize the various appearances of chordoma in FNAB. 相似文献
103.
Lillo C Lea US Leydecker MT Meyer C 《The Plant journal : for cell and molecular biology》2003,35(5):566-573
In wild-type Nicotiana plumbaginifolia and other higher plants, nitrate reductase (NR) is rapidly inactivated/activated in response to dark/light transitions. Inactivation of NR is believed to be caused by phosphorylation at a special conserved regulatory Ser residue, Ser 521, and interactions with divalent cations and inhibitory 14-3-3 proteins. A transgenic N. plumbaginifolia line (S(521)) was constructed where the Ser 521 had been changed by site-directed mutagenesis into Asp. This mutation resulted in complete abolishment of inactivation in response to light/dark transitions or other treatments known to inactivate NR. During prolonged darkness, NR in wild-type plants is in the inactivated form, whereas NR in the S(521) line is always in the active form. Differences in degradation rate between NR from S(521) and lines with non-mutated NR were not found. Kinetic constants like Km values for NADH and NO3(-) were not changed, but a slightly different pH profile was observed for mutated NR as opposed to non-mutated NR. Under optimal growth conditions, the phenotype of the S(521) plants was not different from the wild type (WT). However, when plants were irrigated with high nitrate concentration, 150 mM, the transgenic plants accumulated nitrite in darkness, and young leaves showed chlorosis. 相似文献
104.
Several known outer membrane permeabilizers increased susceptibility of a highly resistant pathogenic strainPseudomonas aeruginosa to different antibiotics and plant extracts. Of all the chemicals tested, EDTA, sodium citrate and sodium hexametaphosphate
(HMP) were found to be potent permeabilizers as shown by enhanced lysis of the bacteria in the presence of lysozyme. In the
presence of EDTA and sodium citrate susceptibility of the strain to gentamicin and rifampicin increased markedly. The strain
was resistant to vancomycin but became susceptible when grown in the presence of increasing amounts of EDTA and sodium citrate.
Similar results were obtained for erythromycin when treated with sodium citrate. EDTA was found to be most potent permeabilizer
in enhancing the activity of the plant extracts. Though HMP was an effective permeabilizer it had a weak or no effect on the
activity of the antibiotics and plant extracts. 相似文献
105.
The copper (II) complex [Cu(Itpy)(2)](ClO(4))(2) (1), (Itpy=imidazole terpyridine) has been synthesized and structurally characterized. Crystal structure of the complex shows the complex to be a monomeric copper (II) species with two Itpy ligands coordinated to the metal ion to give a six coordinate complex. The complex has a distorted octahedral geometry with axial elongation. Variable temperature crystal structure data shows dynamic nature of the Jahn-Teller distortion. The complex is an avid DNA binder with a binding constant of 4.26+/-0.20x10(3)M(-1). Observed changes in the viscosity and circular dichroic spectrum of calf thymus DNA solution in the presence of complex 1 suggests intercalative binding of complex 1 to DNA. The complex cleaves supercoiled pBR322 DNA oxidatively in the presence of hydrogen peroxide. 相似文献
106.
Vijayalakshmi R Subramanian V Nair BU 《Journal of biomolecular structure & dynamics》2002,19(6):1063-1071
Molecular modeling and energy minimisation calculations have been used to investigate the interaction of chromium(III) complexes in different ligand environments with various sequences of B-DNA. The complexes are [Cr(salen)(H(2)O)(2)](+); salen denotes 1, 2 bis-salicylideneaminoethane, [Cr(salprn)(H(2)O)(2)](+); salprn denotes 1, 3 bis- salicylideneaminopropane, [Cr(phen)(3)](3+); phen denotes 1, 10 phenanthroline and [Cr(en)(3)](3+); en denotes ethylenediamine. All the chromium(III) complexes are interacted with the minor groove and major groove of d(AT)(12), d(CGCGAATTCGCG)(2) and d(GC)(12) sequences of DNA. The binding energy and hydrogen bond parameters of DNA-Cr complex adduct in both the groove have been determined using molecular mechanics approach. The binding energy and formation of hydrogen bonds between chromium(III) complex and DNA has shown that all complexes of chromium(III) prefer minor groove interaction as the favourable binding mode. 相似文献
107.
The binding of 3H-physostigmine (3H-Ph) to human and rat plasma proteins and crystalline serum albumin was studied by ultrafiltration technique. This study showed that the percentage of 3H-Ph bound to rat plasma slightly decreased from 49% to 41% whereas human plasma showed an increase in binding from 29% to 43% over a 50-fold increase in drug concentration. Human plasma samples which were collected in a bag coated with citrate phosphate dextrose adenine-1 solution bound 50% less 3H-Ph than samples collected with EDTA indicating a drug-drug interaction between 3H-Ph and anticoagulants. No significant change in binding was observed if the samples were frozen prior to use. Scatchard plots for binding of 3H-Ph resulted in a positive slope for human plasma and a negative slope for rat plasma; whereas curvilinear Scatchard plots with negative slopes were obtained for binding to human and rat crystalline serum albumin. 相似文献
108.
Mohammed Afzal Azam Unni Jayaram 《Journal of enzyme inhibition and medicinal chemistry》2016,31(4):517-526
Alanine racemase is a fold type III PLP-dependent amino acid racemase enzyme catalysing the conversion of l-alanine to d-alanine utilised by bacterial cell wall for peptidoglycan synthesis. As there are no known homologs in humans, it is considered as an excellent antibacterial drug target. The standard inhibitors of this enzyme include O-carbamyl-d-serine, d-cycloserine, chlorovinyl glycine, alafosfalin, etc. d-Cycloserine is indicated for pulmonary and extra pulmonary tuberculosis but therapeutic use of drug is limited due to its severe toxic effects. Toxic effects due to off-target affinities of cycloserine and other substrate analogs have prompted new research efforts to identify alanine racemase inhibitors that are not substrate analogs. In this review, an updated status of known inhibitors of alanine racemase enzyme has been provided which will serve as a rich source of structural information and will be helpful in generating selective and potent inhibitor of alanine racemase. 相似文献
109.
110.
Anna Brzozowska Ruedi Fries James E. Womack Unni Grimholt Ola Myklebost Sissel Rogne 《Mammalian genome》1993,4(1):53-57
The nucleotide sequence data reported in this paper have been submitted to EMBL Data Library and have been assigned the accession number: X64839 Bos taurus mRNA for apoprotein E. 相似文献