Christopher A Straub

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Smac mimetic compounds targeting the inhibitor of apoptosis proteins (IAP) baculoviral IAP repeat-3 domain are presumed to reduce the threshold for apoptotic cell death by alleviating caspase-9 repression. We explored this tenet in an unbiased manner by searching for small interfering RNAs that are able to confer resistance to the Smac mimetic compound(More)
Oncogenic mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in several types of cancer, but the metabolic consequences of these genetic changes are not fully understood. In this study, we performed (13)C metabolic flux analysis on a panel of isogenic cell lines containing heterozygous IDH1/2 mutations. We observed that under hypoxic conditions,(More)
Inhibitor of apoptosis proteins (IAPs) such as XIAP subvert apoptosis by binding and inhibiting caspases. Because occupation of the XIAP BIR3 peptide binding pocket by Smac abolishes the XIAP–caspase 9 interaction, it is a proapoptotic event of great therapeutic interest. An assay for pocket binding was developed based on the displacement of Smac 7-mer from(More)
Growth hormone (GH) is an important regulator of skeletal growth, as well as other adapted processes in salmonids. The GH gene (gh) in salmonids is represented by duplicated, non-allelic isoforms designated as gh1 and gh2. We have isolated and characterized gh-containing bacterial artificial chromosomes (BACs) of both Atlantic and Chinook salmon (Salmo(More)
The complete amino acid sequence of canine miniplasminogen (Mr 36,678, 333 residues) was determined with the aid of fragments obtained by cleavage with BNPS-skatole, cyanogen bromide or clostripain. The fragments were aligned with overlapping sequences. Sequence comparison with miniplasminogens of other species gave identities in the range of 80% (bovine)(More)
The complete amino acid sequence of equine miniplasminogen (Mr 37,132, 338 residues) was determined with the aid of fragments obtained by cleavage with 2-(2-nitrophenylsulfenyl)-3-methyl-3'-bromoindolenine, cyanogen bromide or clostripain. The fragments were aligned with overlapping sequences. Sequence comparison with other species gave identities in the(More)
MELK kinase has been implicated in playing an important role in tumorigenesis. Our previous studies suggested that MELK is involved in the regulation of cell cycle and its genetic depletion leads to growth inhibition in a subset of high MELK-expressing basal-like breast cancer cell lines. Herein we describe the discovery and optimization of novel MELK(More)
Oncogenic mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in several types of cancer, but the metabolic consequences of these genetic changes are not fully understood. In this study, we performed C metabolic flux analysis on a panel of isogenic cell lines containing heterozygous IDH1/2 mutations. We observed that under hypoxic conditions,(More)
While adding the structural features that are more favored by on-target activity is the more common strategy in selectivity optimization, the opposite strategy of subtracting the structural features that contribute more to off-target activity can also be very effective. Reported here is our successful effort of improving the kinase selectivity of type II(More)