Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT01586 (G418)
 2,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study and evaluate the potential of the haematopoietic system as a target for gene therapy in haemophilia A, we have infected murine bone-marrow cells with a recombinant retrovirus encoding blood-coagulation factor VIII and the bacterial enzyme neomycin-phosphotransferase. After transplantation of the infected bone marrow into lethally irradiated mice, the presence of intact vector could be demonstrated in DNA isolated from individual haematopoietic progenitor-cell-derived spleen colonies. About 8% of the spleen colonies were shown to contain the intact vector. Selection for resistance to the neomycin analogue G418 prior to transplantation specifically killed the uninfected bone-marrow cells and, as a result, over 90% of the spleen colonies contained the factor VIII vector. However, expression of factor VIII in vivo, either at the RNA or at the protein level could not be demonstrated. From these data we conclude that: 1) retroviral vectors can be used to transfer factor-VIII cDNA into haematopoietic progenitor cells; 2) the vector sequences are expressed immediately after integration; and 3) transcription of the vector is repressed in the progenitor-cell-derived cells.
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PMID:Toward gene therapy in haemophilia A: retrovirus-mediated transfer of a factor VIII gene into murine haematopoietic progenitor cells. 164 25

The fourth cytoplasmic domain, the so-called C-terminal juxtamembrane segment or helix VIII, has been identified in numerous G-protein-coupled receptors and exhibits unique functional characteristics. Efforts have been devoted to studying the juxtamembrane segment in order to understand the biological importance of the segment in G-protein activation of the cannabinoid CB1 and CB2 receptors. Recent biochemical data revealed that the CB1 C-terminal juxtamembrane peptide fragment CB1-(401-417) can directly activate the G-protein and also showed that the specificity of the signal transduction activation by the C-terminal juxtamembrane region is unique to the CB1 receptor but not to the CB2 receptor (Mukhopadhyay, S., and Howlett, A. C. (2001) Eur. J. Biochem. 268, 499-505). However, there is experimental work, not yet reported, on the conformational analyses and structural comparison between the respective helix VIII segments of the two receptors. In the present study, we have examined the conformational specificities of the cytoplasmic helical domains for both cannabinoid receptors. Three-dimensional structural features of two synthetic CB1 and CB2 peptides, CB1I397-G418 and CB2I298-K319, respectively, in membrane mimetic DPC micelles were studied using a combined high resolution NMR and computer modeling approach. Comparisons of the NMR-determined structures of the two peptides as well as their correspondent mutant peptides revealed their conformational properties and salt bridge dissimilarity, which might help us to understand the different structural roles of the fourth cytoplasmic helices in the function and regulation of CB1 and CB2 receptors.
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PMID:NMR structural comparison of the cytoplasmic juxtamembrane domains of G-protein-coupled CB1 and CB2 receptors in membrane mimetic dodecylphosphocholine micelles. 1555 Mar 82