Identification of 4-amino-4-deoxychorismate synthase as the molecular target for the antimicrobial action of (6s)-6-fluoroshikimate

(6S)-6-Fluoroshikimate has antimicrobial activity. The molecular basis of this effect had not been identified, but there was speculation that (6S)-6-fluoroshikimate is first converted in vivo into 2-fluorochorismate, which then could inhibit 4-amino-4-deoxychorismate synthase (ADCS). 2-Fluorochorismate was prepared from E-fluorophosphoenolpyruvate and erythose-4-phosphate by the sequential reactions of DAHP synthase, dehydroquinate synthase, dehydroquinase, shikimate dehydrogenase, EPSP synthase, and chorismate synthase. Inhibition studies on ADCS showed that it was inhibited rapidly and irreversibly by 2-fluorochorismate. Electrospray mass spectrometry of the inactivated enzyme showed an additional mass of 198 +/- 10 Da. A novel peptide of 1087.6 Da was identified in the HPLC trace for the tryptic digest of 2-fluorochorismate-inactivated ADCS. Sequencing of this peptide by MS/MS showed that the peptide corresponded to residues 272-279 with a modification of 206.1 Da on Lys-274. This observation is particularly exciting in the context of a recent proposal for the catalytic mechanism of ADCS.     

Synthesis and analysis of RNA containing 6-trifluoromethylpurine ribonucleoside

We report the synthesis of a 5'-DMT-2'-TBDMS-protected phosphoramidite of 6-trifluoromethylpurine ribonucleoside ((TFM)P) and its use in the site-specific incorporation of 6-trifluoromethylpurine into RNA. Properties of (TFM)P-substituted RNA suggest it will be valuable in the study of RNA structure and the binding of RNA-modifying enzymes, particularly the RNA-editing adenosine deaminases. Reaction: see text.     

Feasibility of high-frequency field-modulation for Zeeman-modulated atomic-absorption spectrometers

Some advantages of alternating field modulation for Zeeman background-correction are discussed. A technique for applying such modulation to a conventional hollow-cathode lamp is examined. The technique is used to provide a very simple conversion of a Techtron AA3 spectrometer to Zeeman background-corrected operation.     

Determination of molecular structure in solution using vibrational circular dichroism spectroscopy: the supramolecular tetramer of S-2,2'-dimethyl-biphenyl-6,6'-dicarboxylic acid

The infrared (IR) and vibrational circular dichroism (VCD) spectra of S-2,2'-dimethyl-biphenyl-6,6'-dicarboxylic acid, S-1, in CDCl(3) solution are concentration-dependent, showing that oligomerization occurs with increasing concentration. DFT calculations support the conclusion that the oligomer formed is the cyclic tetramer (S-1)(4), in which S-1 monomers are linked by hydrogen(H)-bonded (COOH)(2) moieties. Due to the existence of two inequivalent tautomeric conformations of each (COOH)(2) moiety, six inequivalent conformations of (S-1)(4) are possible. B3LYP/6-31G* DFT calculations predict that the conformation "aaab", possessing three equivalent (COOH)(2) conformations, a, and one tautomeric conformation, b, has the lowest free energy. B3LYP/6-31G* IR and VCD spectra vary substantially with conformation. The B3LYP/6-31G* IR and VCD spectra of the C=O stretch modes of "aaab" are in excellent agreement with the experimental spectra, while those of all other conformations exhibit poor agreement, confirming the prediction that the "aaab" conformation is the predominant conformation. Comparison of the calculated IR and VCD spectra of the six conformations to the experimental spectra in the range 1100-1600 cm(-1) further supports this conclusion. The study is the first to use VCD spectroscopy to determine the structure of a supramolecular species.     

Synthesis of novel heterocycles from 2-amino-3-(cyanomethylsulfonyl)thiophene

The synthesis and selected reactions of 2-amino-3-(cyanomethylsulfonyl)thiophene is reported. In particular, cyclization reaction of the versatile aminothiophene yielded a number of novel thieno[3,2-b][1,4]-thiazine 1,1-dioxides, as well as the analogous thieno[2,3-e][1,3,4]thiadiazine 4,4-dioxide. Reaction of the thienothiazine system with hydrazine was subsequently explored, which resulted in either ring-opening of the thiazine and formation of an aminopyrazole or solely ring cleavage depending on the thiazine substituent. Additionally, the synthesis of bis(2-amino-3-thienyl)sulfone and the corresponding bis-acetamide is described.     

Application of the zeeman effect to analytical atomic spectroscopy-III Extension of calibration curves

An application of the Zeeman effect is described by which calibration curves applicable to high analyte concentrations may be obtained. The procedure uses single-beam measurements on the displaced σ-components of the Zeeman multiplet, and thus permits controlled desensitization of an atomic-absorption signal to be obtained, simply by increasing the magnetic field strength, while leaving the monochromator permanently set on the optimum analytical line for the element considered. Calibration curves for Ca, Cd and Cu are given for applied field strengths from 0 to 16kG.     

Superdeformed bands in195Tl

Two superdeformed (SD) bands have been found and assigned to¹⁹⁵Tl on the basis of excitation function and cross bombardment results. The two bands are almost identical in transition energies to those observed in¹⁹³Tl. They are signature partners with a splitting, presumably due to the proton i_13/2 (=5/2) orbital, characteristic of all known SD bands in the thallium isotopes. Their alignments relative to the¹⁹³Tl bands were found to be zero.On leave from Comision National de Energia Atomica 1429 Buenos Aires, Argentina.     

Aminosulf(ox)ides as ligands for Iridium(I)-catalyzed asymmetric transfer hydrogenation

A new class of efficient catalysts was developed for the asymmetric transfer hydrogenation of unsymmetrical ketones. A series of chiral N,S-chelates (6-22) was synthesized to serve as ligands in the iridium(I)-catalyzed reduction of ketones. Both formic acid and 2-propanol proved to be suitable as hydrogen donors. Sulfoxidation of an (R)-cysteine-based aminosulfide provided a diastereomeric ligand family containing a chiral sulfur atom. The two chiral centers of these ligands showed a clear effect of chiral cooperativity. In addition, aminosulfides containing two asymmetric carbon atoms in the backbone were synthesized. Both the sulfoxide-containing beta-amino alcohols and the aminosulfides derived from 1,2-disubstituted amino alcohols gave rise to high reaction rates and moderate to excellent enantioselectivities in the reduction of various ketones. The enantioselective outcome of the reaction was favorably affected by selecting the most appropriate hydrogen donor. Enantioselectivities of up to 97% were reached in the reduction of aryl-alkyl ketones.     

Microsoft Excel as a supplement in a high school statistics course

This study was conducted in the spring of 2002 at Arlington High School in a Probability and Statistics course for junior and senior level students. Two sections of the class were compared with respect to the use/non-use of EXCEL in the course. The experimental group (the one using EXCEL) outperformed the control group on five of the six teacher-created unit tests and on both of the criterion referenced assessments used by the district; however, the differences were not statistically significant at the 0.05 level. Furthermore, the experimental group expressed very positive feelings towards the use of the software in a survey administered at the conclusion of the course.