Fas Ligand (FasL) binds to the Fas receptor to induce apoptosis or activate other signaling pathways. FasL can also transduce "reverse signals" and thus participate in bidirectional signaling. The FasL intracellular domain contains consensus sequences for phosphorylation and a proline rich protein interaction domain. This latter region of FasL has previously been implicated in FasL reverse signaling and regulation of FasL surface expression. In this report, we sought to identify novel FasL interacting proteins to help understand signaling through and trafficking of this death factor. Using mass spectrometry, we identified sorting nexin 18, adaptin beta, Grb2, PACSIN2 and PACSIN3 as FasL interacting proteins. RNAi mediated knockdown of Grb2 significantly reduced the surface expression of FasL and increased its expression intracellularly. Our data show that Grb2 controls the subcellular localization of FasL. All other proteins identified in our screen could be classified as trafficking-associated proteins, highlighting the complex regulation of the surface expression of this death factor.

This thesis focuses on the properties of the diiminepyridine (DIP) ligand and its transition metal complexes, especially cobalt complexes. Existing and new X-ray structures of five-coordinate DIP Fe and Co dihalide complexes have been analyzed using the two-angle criterion ω. Substituent effects (less than 6 kcal/mol) and metal effects (mostly less than 6 kcal/mol) on structure distortion have been explored by density functional theory (DFT). The small energy barrier indicated easy distortion of the coordination geometries. The same strategy was also applied to the analysis of iron dialkyl complexes. There seems to be no direct correlation between structural preference and catalytic activity in olefin polymerization. Ligand parameters of DIP-type ligands, which intend to measure the σ-donor and π-acceptor ability, were developed using DFT calculation. The stabilization energy of the metal complexes was decomposed assuming a linear energy relationship. The results showed that the standard DIP ligand is both a strong σ-donor and a strong π-acceptor, and inferior only to the bis(carbene)pyridine ligand. A mild way to make (DIP)CoR using labile-ligand cobalt dialkyl precursors has been explored. A simple and easy way to synthesize (Py)2Co(CH2SiMe3)2 has been developed. This compound is stable at room temperature and can be further converted to (TMEDA)Co(CH2SiMe3)2 in high yield. The X-ray structure of the analogous (Py)2Co(CH2CMe2Ph)2 showed a structure similar to its iron analog. Application to DIP ligands indicates that the π-acceptor ability of the ligand determines whether cobalt(I) or cobalt(II) dialkyl will be obtained. However, steric protection is important in obtaining stable cobalt(I) alkyl complexes. Hydrogenolysis of LCoCH2SiMe3 (L: 2,6-[2,6-Me2C6H3N=C(CH3)]2C5H3N) generated LCo(N2) complex in the presence of dinitrogen. When reacted with organic halides, especially aryl chlorides, LCo(N2) broke the carbon-halogen bond through a binuclear oxidative addition mode to generate two cobalt(I) products. The radical mechanism proposed was supported by DFT studies. The resulting cobalt(I) aryl products can further react with activated alkyl halides to generate cross-coupled products, probably also through a radical mechanism. LCo(N2) can also be used to break the acyl carbon-oxygen bond of esters, although less efficiently.

No description available.

This thesis focuses on the properties of the diiminepyridine (DIP) ligand and its transition metal complexes, especially cobalt complexes. Existing and new X-ray structures of five-coordinate DIP Fe and Co dihalide complexes have been analyzed using the two-angle criterion ω. Substituent effects (less than 6 kcal/mol) and metal effects (mostly less than 6 kcal/mol) on structure distortion have been explored by density functional theory (DFT). The small energy barrier indicated easy distortion of the coordination geometries. The same strategy was also applied to the analysis of iron dialkyl complexes. There seems to be no direct correlation between structural preference and catalytic activity in olefin polymerization. Ligand parameters of DIP-type ligands, which intend to measure the σ-donor and π-acceptor ability, were developed using DFT calculation. The stabilization energy of the metal complexes was decomposed assuming a linear energy relationship. The results showed that the standard DIP ligand is both a strong σ-donor and a strong π-acceptor, and inferior only to the bis(carbene)pyridine ligand. A mild way to make (DIP)CoR using labile-ligand cobalt dialkyl precursors has been explored. A simple and easy way to synthesize (Py)2Co(CH2SiMe3)2 has been developed. This compound is stable at room temperature and can be further converted to (TMEDA)Co(CH2SiMe3)2 in high yield. The X-ray structure of the analogous (Py)2Co(CH2CMe2Ph)2 showed a structure similar to its iron analog. Application to DIP ligands indicates that the π-acceptor ability of the ligand determines whether cobalt(I) or cobalt(II) dialkyl will be obtained. However, steric protection is important in obtaining stable cobalt(I) alkyl complexes. Hydrogenolysis of LCoCH2SiMe3 (L: 2,6-[2,6-Me2C6H3N=C(CH3)]2C5H3N) generated LCo(N2) complex in the presence of dinitrogen. When reacted with organic halides, especially aryl chlorides, LCo(N2) broke the carbon-halogen bond through a binuclear oxidative addition mode to generate two cobalt(I) products. The radical mechanism proposed was supported by DFT studies. The resulting cobalt(I) aryl products can further react with activated alkyl halides to generate cross-coupled products, probably also through a radical mechanism. LCo(N2) can also be used to break the acyl carbon-oxygen bond of esters, although less efficiently.

Thesis (Ph. D.)--University of Texas at Austin, 2007. / Vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 82-102).

Thesis (Ph. D.)--University of North Texas, Aug., 2007. / Title from title page display. Includes bibliographical references.

Proefschrift Universiteit van Amsterdam. / Auteursnaam op omslag: Kiki Tesselaar. Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

Thesis (Ph.D.)--University of Melbourne, Dept. of Medical Biology, 2002. / Typescript (photocopy). Includes bibliographical references.

Zugl.: Stuttgart, Univ., Diss., 2006