Robert Martone

Covance

Surprising study suggests experiences while young cause the brain to experience changes to the genome

A novel mass spectrometry-based workflow for de novo sequencing of a full-length monoclonal antibody (LB509) against α-synuclein is presented. This approach combines chemical modification of cysteine residues, multiple enzymatic digestion, stable isotope labeled amino acids in cell culture (SILAC), liquid chromatography coupled tandem mass spectrom...

SAR on HTS hits 1 and 2 led to the potent, Notch-1-sparing GSI 9, which lowered brain Abeta in Tg2576 mice at 100 mg/kg po. Converting the metabolically labile methyl groups in 9 to trifluoromethyl groups afforded the more stable analogue 10, which had improved in vivo potency. Further side chain modification afforded the potent Notch-1-sparing GSI...

Using a cell-based assay, we have identified a new series of Notch-sparing gamma-secretase inhibitors from HTS screening leads 2a and 2e. Lead optimization studies led to the discovery of analog 8e with improved gamma-secretase inhibitory potency and Notch-sparing selectivity.

The CompacT SelecT is the latest generation automated cell culture system in the SelecT product line allowing incubation of up to 90 T-175 flasks and preparation of 210 assay-ready plates. We have successfully implemented the CompacT SelecT in support of a number of cell-based assays used in our Alzheimer's disease (AD) lead optimization programs....

Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which numerous mouse models have been generated. In both AD patients and mouse models, there is increasing evidence that neuronal dysfunction occurs before the accumulation of β-amyloid (Aβ)-containing plaques and neurodegeneration. Characterization of the timing and nature of...

Alzheimer's disease (AD) is a debilitating disease widely thought to be associated with the accumulation of beta amyloid (Abeta) in the brain. Inhibition of gamma-secretase, one of the enzymes responsible for Abeta production, may be a useful strategy for the treatment of AD. Described below is a series of gamma-secretase inhibitors designed from a...

Time is a fundamental property of the physical world. Because time encompasses the antinomic qualities of transience and duration, the definition of time poses a dilemma for the formulation of a comprehensive physical theory. The partial elimination of time is a common solution to this dilemma. In his mechanical philosophy, Newton appears to resort...

In familial amyloidotic polyneuropathy, transthyretin (TTR)-amyloid is deposited in peripheral nerve (PN) and frequently in ocular vitreous. We explored the possiblity that a common factor may be implicated in amyloidogenesis in these two tissues. We studied the PN myelin protein, P2, which shares conformational homology with serum retinol-binding...