Millipore Sigma Vibrant Logo
 

a0281


16 Results Advanced Search  
Showing
Products (0)
Documents (16)
Site Content (0)

Narrow Your Results Use the filters below to refine your search

Document Type

  • (11)
  • (3)
  • (2)
Can't Find What You're Looking For?
Contact Customer Service

 

  • NU050/32-211-AAM200281

    Document Type:
    Certificate of Quality
    Lot Number:
    AAM200281
    Product Catalog Number:
    NU050/32-211
    Product Catalog Name:
    NovAseptic Valve, Valve Body, Flow through 180˚

  • NU050/31-211-AAN200281

    Document Type:
    Certificate of Quality
    Lot Number:
    AAN200281
    Product Catalog Number:
    NU050/31-211
    Product Catalog Name:
    NovAseptic Valve, Valve Body, Shut off 90˚

  • Novel {gamma}-secretase inhibitors uncover a common nucleotide-binding site in JAK3, SIRT2, and PS1. 20237298

    gamma-Secretase is an intramembrane-cleaving protease responsible for the final proteolytic event in the production of the amyloid-beta peptides (Abeta) implicated in Alzheimer's disease (AD). Inhibition of gamma-secretase activity is thus an attractive therapeutic strategy to slow down the pathogenesis of AD. Drugs often target more than one biomolecule because of conserved 3-dimensional structures in prospective protein binding sites. We have capitalized on this phenomenon of nature to identify new gamma-secretase inhibitors. Here we show that 2-hydroxy naphthyl derivatives, a previously identified subclass of NAD(+) analog inhibitors of sirtuin 2 (SIRT2), are direct gamma-secretase inhibitors. Subsequent structure-activity relationship studies further showed that 2-hydroxy-1-naphthaldehyde is the minimal pharmacophore for gamma-secretase inhibition. In evaluating target protein determinants of inhibition, we identified a common GXG signature nucleotide-binding site (NBS) shared by the gamma-secretase subunit presenilin-1 C-terminal fragment (PS1-CTF), SIRT2, and Janus kinase 3 (JAK3). Because a detailed 3-dimensional structure of gamma-secretase is beyond our knowledge, we took advantage of the known crystal structure of human JAK3 to model the NBS of the PS1-CTF, which includes the catalytic residue D385. Our results suggest that the flexible PS1-CTF (381)LGLG(384) loop comprises a substrate-docking site capable of recognizing specifically different gamma-secretase substrates.-Wu, F., Schweizer, C., Rudinskiy, N., Taylor, D. M., Kazantsev, A., Luthi-Carter, R., Fraering, P. C. Novel gamma-secretase inhibitors uncover a common nucleotide-binding site in JAK3, SIRT2, and PS1.
    Document Type:
    Reference
    Product Catalog Number:
    Multiple
    Product Catalog Name:
    Multiple

  • Generation of Monoclonal Antibody Fragments Binding the Native γ-Secretase Complex for Use in Structural Studies. 23066899

    A detailed understanding of γ-secretase structure is crucially needed to elucidate its unique properties of intramembrane protein cleavage and to design therapeutic compounds for the safe treatment of Alzheimer's disease. γ-Secretase is an enzyme complex composed of four membrane proteins, and the scarcity of its supply associated with the challenges of crystallizing membrane proteins is a major hurdle for the determination of its high-resolution structure. This study addresses some of these issues, first by adapting CHO cells overexpressing γ-secretase to growth in suspension, thus yielding multiliter cultures and milligram quantities of highly purified, active γ-secretase. Next, the amounts of γ-secretase were sufficient for immunization of mice and allowed generation of Nicastrin- and Aph-1-specific monoclonal antibodies, from which Fab fragments were proteolytically prepared and subsequently purified. The amounts of γ-secretase produced are compatible with robot-assisted crystallogenesis using nanoliter technologies. In addition, our Fab fragments bind exposed regions of native γ-secretase in a dose-dependent manner without interfering with its catalytic properties and can therefore be used as specific tools to facilitate crystal formation.
    Document Type:
    Reference
    Product Catalog Number:
    MAB1563
    Product Catalog Name:
    Anti-Presenilin-1 Antibody, NT, clone hPS1-NT