Thesis (Ph. D.)--University of Illinois, 1919. / Vita. Bibliography: p. 45-46.

Thesis (Ph. D.)--University of Illinois, 1919. / Vita. Bibliography: p. 45-46.

No description available.

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (leaves 175-194).

Thesis (Ph.D.) - University of St Andrews, September 2009. / Electronic version restricted until 21st September 2010.

In biotechnology and drug delivery silica materials are of interest but the controlled generation of silicic acid is difficult. To get more insight into the molecular mechanisms that control biosilification, it is important to study the proteins involved in this process. The sponge protein silicatein α synthesises part of the axial filament in the spicules which in situ polymerises silicic acid. It has been demonstrated that the polymerisation of siloxanes such as for example tetraethoxysilane (TEOS) can be carried out by both wild type and recombinant silicatein α. Unfortunately, it has not been possible yet to get reasonable amounts of wild type or recombinant silicatein α to perform biophysical studies. The human cysteine protease cathepsin L has almost 50 % identical residues with silicatein α. To get more insight into the mechanism of silica polymerisation, cathepsin L mutants were generated by our collaborators. Those mutants show sequence features and activity specific for silicatein α. The X-ray structure of one of those mutants (mutant 4SER) to 1.5 Å has allowed us to propose a new chemical mechanism for the catalysis of silicic acid polymerisation. ADP-β-D-glycero-D-mannoheptose and ADP-β-L-glycero-D-mannoheptose are interconverted by the SDR-enzyme ADP-β-L-glycero-D-mannoheptose 6-epimerase (AGME). This epimerisation reaction is the final reaction in the biosynthetic route of the precursor of heptose. Heptose is a part of the inner core of the lipopolysaccharide in Gram-negative bacteria. In mutants which do not have heptose, nonpolar compounds can penetrate more easily through the outer membrane. These mutants also show less pathogenicity. As a consequence the lipopolysaccharide biosynthetic pathway represents an interesting target for antimicrobial compounds. The crystal structure of AGME in complex with ADP-α-glucose has already been solved. From this structure a catalytic mechanism for this enzyme has been proposed with Tyr140 and Lys178 operating as acid/base residues. The disordered nature of the nucleotide sugar’s glucose moiety in the previous structure due to the wrong configuration of the sugar has hindered assignment of a mechanism. The determination of the X-ray structure of AGME Y140F in complex with a substrate in the β-manno configuration (ADP-β-mannose) to 2.4 Å resolution has given new insight into the mechanism of this SDR enzyme. A mechanism is proposed with only Tyr140 operating as catalytic acid/base. Initially it was thought that MMP-3 participates in the synovitis cascade. Glycoproteins, several parts of the ECM such as fibronectin and laminin and also collagens and procollagens are targets of this matrixin. Furthermore MMP-3 can undergo autocatalysis and is also able to cleave a range of other members of the matrixin family. Matrixins also play an important role in diseases such as cancer, rheumatoid arthritis and osteoporosis. This makes them targets for inhibitor design. Many structures of matrix metalloproteinases, such as stromelysin-1, in complex with various inhibitors have already been solved. The structures of the catalytic domain of MMP-3 in complex with two nonpeptide inhibitors are discussed.

In this project the author has attempted to determine the specific conductance of a gel of known composition; the changes, if any, of conductance in a gel as it sets; and the changes in conductance due to the diffusing of an electrolyte through the gel.

Observation of crystal growths resulting from the chemical interaction of stannous chloride and sodium arsenate in silicic acid gels revealed the following very interesting fact. Gels identical in every respect except acidity, contained crystal growths varying greatly in appearance. The purpose of this investigation was, therefore, to allow stannous and arsenate ion to combine in a series of accurately prepared gels, identical in all respects except the acid content, and to observe the effect upon crystal growth of: (1) varying the acid concentration; and (2) varying the kind of acid

Chapter I: Statement of the Problem The purpose of this investigation was to determine to what extent the reaction between stannous and arsenate ions in silicic acid gels is influenced by temperature. This was to be done by observing (1) the rate of crystal growth; and (2) the appearance of the crystal growth in sets of gels identical in composition but kept at different temperatures throughout the process of crystal growth.

The adsorption behavior of silicic acid and arsenite alone and competitively on goethite over a broad pH range (3-11) at environmentally relevant concentrations was investigated utilizing pH adsorption data and zeta potential measurements. Both addition scenarios (Si before As(III) and As(III) before Si) were examined. The results of the adsorption experiments and zeta potential measurements were then used to model the single ion and competitive ion adsorption on goethite with the CD-MUSIC model implemented in the FITEQL 4.0 computer program. Silicic acid adsorption was reduced by the presence of arsenite for all but one of the adsorption scenarios examined, while in contrast silicic acid had little effect upon arsenite adsorption. However, the presence of silicic acid, regardless of the addition scenario, dramatically increased the arsenite equilibrium solution concentration over the entire pH range investigated. The CD-MUSIC model was able to predict the single ion adsorption behavior of silicic acid and arsenite on goethite. The modeled zeta potential data provided further evidence of the CD-MUSIC model's ability to describe the single anion adsorption on goethite. Our model was also able to collectively describe adsorption and zeta potential data for the low Si-arsenite adsorption scenario quite well however, our model under-predicted silicic acid adsorption for the high Si-arsenite competitive scenario. / Master of Science