Model Studies on Peroxidic Glutathione Transferase (GST) Inhibitors: C5-Methylated 1,2,4-Trioxanes with C6-Acrylate Side Chains

2015 ◽  
Vol 2015 (20) ◽  
pp. 4349-4352 ◽  
Author(s):  
Axel G. Griesbeck ◽  
Andreas Maaßen ◽  
Maria Bräutigam ◽  
Markus Pietsch
Keyword(s):  
Glutathione Transferase ◽  
Side Chains ◽  
Model Studies

ChemInform Abstract: Model Studies on Peroxidic Glutathione Transferase (GST) Inhibitors: C5-Methylated 1,2,4-Trioxanes with C6-Acrylate Side Chains.

ChemInform ◽  
2015 ◽  
Vol 46 (47) ◽  
pp. no-no
Author(s):  
Axel G. Griesbeck ◽  
Andreas Maassen ◽  
Maria Braeutigam ◽  
Markus Pietsch
Keyword(s):  
Glutathione Transferase ◽  
Side Chains ◽  
Abstract Model ◽  
Model Studies

Adaptor protein Lnk associates with Tyr568 in c-Kit

2008 ◽  
Vol 415 (2) ◽  
pp. 241-245 ◽  
Author(s):  
Saskia Gueller ◽  
Sigal Gery ◽  
Verena Nowak ◽  
Liqin Liu ◽  
Hubert Serve ◽  
...  
Keyword(s):  
Binding Site ◽  
Glutathione Transferase ◽  
Critical Role ◽  
Adaptor Protein ◽  
Sh2 Domain ◽  
Erythropoietin Receptor ◽  
Cytokine Receptors ◽  
Juxtamembrane Domain ◽  
Model Studies ◽  
Haemopoietic Cells

The adaptor protein Lnk is expressed in haemopoietic cells and plays a critical role in haemopoiesis. Animal model studies demonstrated that Lnk acts as a broad inhibitor of signalling pathways in haemopoietic lineages. Lnk belongs to a family of proteins sharing several structural motifs, including an SH2 (Src homology 2) domain which binds phosphotyrosine residues in various signal-transducing proteins. The SH2 domain is essential for Lnk-mediated negative regulation of several cytokine receptors [e.g. Mpl, EpoR (erythropoietin receptor), c-Kit]. Therefore inhibition of the binding of Lnk to cytokine receptors might lead to enhanced downstream signalling of the receptor and thereby to improved haemopoiesis in response to exposure to cytokines (e.g. erythropoietin in anaemic patients). This hypothesis led us to define the exact binding site of Lnk to the stem cell factor receptor c-Kit. Pull-down experiments using GST (glutathione transferase)-fusion proteins of the different domains of c-Kit showed that Lnk almost exclusively binds to the phosphorylated juxtamembrane domain. Binding of Lnk to the juxtamembrane domain was abolished by point mutation of Tyr568 and was competed by peptides with a phosphotyrosine residue at position 568. Co-immunoprecipitation with full-length wild-type or Y568F mutant c-Kit and Lnk confirmed these results, thus showing the importance of this phosphorylated tyrosine residue. Lnk bound directly to c-Kit without requiring other interacting partners. The identification of the binding site of Lnk to c-Kit will be useful to discover inhibitory molecules that prevent the binding of these two proteins, thus making haemopoietic cells more sensitive to growth factors.

Model Studies on the Construction of Side Chains for CD Intermediates of Vitamin D

1995 ◽  
Vol 48 (3) ◽  
pp. 663 ◽  
Author(s):  
WA Loughlin ◽  
RK Haynes
Keyword(s):  
Vitamin D ◽  
Phosphine Oxide ◽  
Side Chains ◽  
Diphenylphosphine Oxide ◽  
Model Studies

Application of Horner- Wittig methodology for the synthesis of vitamin D side chains was examined through selected model studies. A requirement for syn or threo α- hydroxy diphenylphosphine oxide intermediates was established. The successful conversion of the model phosphine oxide (7) into the alkene (13), which demonstrates the potential of this method, is described.

“In vitro” and in Animal Model Studies on a Double Virus- Inactivated Factor VIII Concentrate

1995 ◽  
Vol 74 (03) ◽  
pp. 868-873 ◽  
Author(s):  
Silvana Arrighi ◽  
Roberta Rossi ◽  
Maria Giuseppina Borri ◽  
Vladimir Lesnikov ◽  
Marina Lesnikov ◽  
...  
Keyword(s):  
Heat Treatment ◽  
Animal Model ◽  
Factor Viii ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Virus Inactivation ◽  
Enveloped Viruses ◽  
Model Studies ◽  
Heat Treated

SummaryTo improve the safety of plasma derived factor VIII (FVIII) concentrate, we introduced a final super heat treatment (100° C for 30 min) as additional virus inactivation step applied to a lyophilized, highly purified FVIII concentrate (100 IU/mg of proteins) already virus inactivated using the solvent/detergent (SID) method during the manufacturing process.The efficiency of the super heat treatment was demonstrated in inactivating two non-lipid enveloped viruses (Hepatitis A virus and Poliovirus 1). The loss of FVIII procoagulant activity during the super heat treatment was of about 15%, estimated both by clotting and chromogenic assays. No substantial changes were observed in physical, biochemical and immunological characteristics of the heat treated FVIII concentrate in comparison with those of the FVIII before heat treatment.

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