7 research outputs found
Focused Ion Beam Fabrication
Contains reports on thirteen research projects and a list of publications.Defense Advanced Research Projects Agency/U.S. Army Research Office Contract DAAL03-88-K-0108National Science Foundation Grant ECS 89-21728MIT Lincoln Laboratory Innovative Research ProgramSEMATECH Contract 90-MC-503Micrion Contract M08774U.S. Army Research Office Contract DAAL03-87-K-0126IBM Corporatio
An x-ray diffraction study of the structure of glass.
Massachusetts Institute of Technology. Dept. of Physics. Thesis. 1968. Ph.D.Page 106 inverted. Vita.Bibliography: leaves 112-115.Ph.D
Role of glutathione transferases in the mechanism of brostallicin activation
Brostallicin is a novel and unique glutathione transferase-activated pro-drug with promising anticancer activity, currently in phase I and II clinical evaluation. In this work, we show that, in comparison with the parental cell line showing low GST levels, the cytotoxic activity of brostallicin is significantly enhanced in the human breast carcinoma MCF-7 cell line, transfected with either human GST-π or GST-μ. Moreover, we describe in detail the interaction of brostallicin with GSH in the presence of GSTP1-1 and GSTM2-2, the predominant GST isoenzymes found within tumor cells. The experiments reported here indicate that brostallicin binds reversibly to both isoenzymes with Kd values in the micromolar range (the affinity being higher for GSTM2-2). Direct evidence that both GSTP1-1 and GSTM2-2 isoenzymes catalyze the Michael addition reaction of GSH to brostallicin has been obtained both by an HPLC-MS technique and by a new fluorometric assay. We also saw the rapid formation of an intermediate reactive species, which is slowly converted into the final products. This intermediate, identified as the R-chloroamido derivative of the GSH-brostallicin adduct, is able to alkylate DNA in a sequence-specific manner and appears to be the active form of the drug. The kinetic behavior of the reaction between brostallicin and GSH, catalyzed by GSTP1-1, has been studied in detail, and a minimum kinetic scheme that suitably describes the experimental data is provided. Overall, these data fully support and extend the findings that brostallicin could be indicated for the treatment of tumor overexpressing the pi or mu class GST
Looking at Human Cytosolic Sialidase NEU2 Structural Features with an Interdisciplinary Approach
Circular dichroism (CD) spectra at
variable temperatures have been
recorded for human cytosolic sialidase NEU2 in buffered water solutions
and in the presence of divalent cations. The results show the prevalence
of β-strands together with a considerable amount of α-helical
structure, while in the solid state, from both previous X-ray diffraction
analysis and our CD data on film samples, the content of β-strands
is higher. In solution, a significant change in CD spectra occurs
with an increase in temperature, related to a decrease in α-helix
content and a slight increase in β-strand content. In the same
range of temperatures, the enzymatic activity decreases. Although
the overall structure of the protein appears to be particularly stable,
molecular dynamics simulations performed at various temperatures evidence
local conformational changes possibly relevant for explaining the
relative lability of enzymatic activity