1,3,5-Triazepane-2,6-diones as structurally diverse and conformationally constrained dipeptide mimetics: identification of malaria liver stage inhibitors from a small pilot library

The development of the 1,3,5-triazepane-2,6-dione system as a novel, conformationally restricted, and readily accessible class of dipeptidomimetics is reported. The synthesis of the densely functionalized 1,3,5-triazepane-2,6-dione skeleton was achieved in only four steps from a variety of simple linear dipeptide precursors. To extend the practical value of 1,3,5-triazepane-2,6-diones, a general polymer-assisted solution-phase synthesis approach amenable to library production in a multiparallel format was developed. The conformational preferences of the 1,3,5-triazepane-2,6-dione skeleton were investigated in detail by NMR spectroscopy and X-ray diffraction. The ring exhibits a characteristic folded conformation which was compared to that of related dipeptide-derived scaffolds including the more planar 2,5-diketopiperazine (DKP). Molecular and structural diversity was increased further through post-cyclization appending operations at urea nitrogens. Preliminary biological screens of a small collection of 1,3,5-triazepane-2,6-diones revealed inhibitors of the underexplored malaria liver stage and suggest strong potential for this dipeptide-derived scaffold to interfere with and to modulate biological pathways.     

Finite element approximation of a model for phase separation of a multi-component alloy with a concentration-dependent mobility matrix

We consider a model for phase separation of a multi-componentalloy with a concentration-dependent mobility matrix and logarithmicfree energy. In particular we prove that there exists a uniquesolution for sufficiently smooth initial data. Further, we provean error bound for a fully practical piecewise linear finiteelement approximation in one and two space dimensions. Finallynumerical experiments with three components in one space dimensionare presented.     

Investigation of the quantitative properties of the quadrupole orthogonal acceleration time-of-flight mass spectrometer with electrospray ionisation using 3,4-methylenedioxymethamphetamine

This paper describes the investigation of the potential of a quadrupole orthogonal acceleration time-of-flight mass spectrometer (Q-TOF) equipped with an atmospheric pressure ionisation interface for quantitative measurements of small molecules separated by reversed phase liquid chromatography. To this end, the detection limits and linear dynamic range in particular were studied in an LC/MS/MS experiment using 3,4-methylenedioxymethamphetamine standards and 3,4-methylenedioxyethylamphetamine for internal standardisation. In a second phase, the experiment was repeated with real biological extracts (whole blood, serum, and vitreous humour). A calibration for 3,4-methylenedioxymethamphetamine and its metabolite 3,4-methylenedioxyamphetamine was prepared in each of these matrices again using 3,4-methylenedioxyethylamphetamine as internal standard. The resulting quantitative data were compared with those obtained by liquid chromatography with fluorescence detection for the same extracts. The Q-TOF results revealed excellent sensitivity and a linear dynamic range of nearly four decades (2-10 000 pg on-column, r(2) = 0.9998, 1/x weighting). Furthermore, all the calibration curves prepared in biological material were superimposable, LC/MS/MS and LC-fluorescence, and the quantitative results for actual samples compared very favourably. It was concluded that the Q-TOF achieves a linear dynamic range for quantitative LC/MS/MS work exceeding that of fluorescence detection and at much better absolute sensitivity. Copyright 1999 John Wiley & Sons, Ltd.     

Measurement of the decay amplitudes of B0 --> J/psiK*0 and B(s)(0) --> J/psistraight phi decays

An angular analysis of B0-->J/psiK(*0) and B(0)(s)-->J/psistraight phi has been used to determine the decay amplitudes with parity-even longitudinal ( A0) and transverse ( A( parallel)) polarization and parity-odd transverse ( A( perpendicular)) polarization. The measurements are based on 190 B0 and 40 B(0)(s) candidates obtained from 89 pb(-1) of &pmacr;p collisions at the Fermilab Tevatron. The longitudinal decay amplitude dominates with |A0|(2) = 0.59+/-0. 06+/-0.01 for B0 and |A0|(2) = 0.61+/-0.14+/-0.02 for B(0)(s) decays. The parity-odd amplitude is found to be small with |A( perpendicular)|(2) = 0.13(+0.12)(-0.09)+/-0.06 for B0 and |A( perpendicular)|(2) = 0.23+/-0.19+/-0.04 for B(0)(s) decays.     

Search for new particles decaying to t&tmacr; in p&pmacr; collisions at radicals = 1.8 TeV

We use 106 pb (-1) of data collected with the Collider Detector at Fermilab to search for narrow-width, vector particles decaying to a top and an antitop quark. Model independent upper limits on the cross section for narrow, vector resonances decaying to t&tmacr; are presented. At the 95% confidence level, we exclude the existence of a leptophobic Z' boson in a model of top-color-assisted technicolor with mass M(Z')<480 GeV/c(2) for natural width gamma = 0.012M(Z'), and M(Z')<780 GeV/c(2) for gamma = 0.04M(Z').     

Search for second and third generation leptoquarks including production via technicolor interactions in p&pmacr; collisions at radicals = 1.8 TeV

We report the results of a search for second and third generation leptoquarks using 88 pb(-1) of data recorded by the Collider Detector at Fermilab. Color triplet technipions, which play the role of scalar leptoquarks, are investigated due to their potential production in decays of strongly coupled color octet technirhos. Events with a signature of two heavy flavor jets and missing energy may indicate the decay of a second (third) generation leptoquark to a charm (bottom) quark and a neutrino. As the data are found to be consistent with standard model expectations, mass limits are determined.