Skip to search formSkip to main contentSkip to account menu
C-terminal Fragment of Presenilin Is the Molecular Target of a Dipeptidic γ-Secretase-specific Inhibitor DAPT (N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-Butyl Ester)*
TLDR
It is shown that one of the major γ-secretase inhibitors of dipeptidic type, N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT), targets the C-terminal fragment of PS by designing and synthesizing DAP-BpB, a photoactivable DAPT derivative.
View on Publisher
Activity-Dependent Proteolytic Cleavage of Neuroligin-1
View on Elsevier
BACE1 activity is modulated by cell-associated sphingosine-1-phosphate
TLDR
It is shown that the activity of β-site APP cleaving enzyme-1 (BACE1), the rate-limiting enzyme for amyloid-β peptide production, is modulated by S1P in mouse neurons, suggesting that cellular S1p directly modulates BACE1 activity.
View on Wiley
Sulindac Sulfide Is a Noncompetitive γ-Secretase Inhibitor That Preferentially Reduces Aβ42 Generation*
TLDR
It is shown that sulindac sulfide (SSide) directly acts on γ-secretase and preferentially inhibits the γ42- secretase activity derived from the 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate-solubilized membrane fractions of HeLa cells, in an in vitroγ-secret enzyme assay.
View on Publisher
Sulindac sulfide is a noncompetitive gamma-secretase inhibitor that preferentially reduces Abeta 42 generation.
TLDR
It is shown that sulindac sulfide (SSide) directly acts on gamma- secretase and preferentially inhibits the gamma(42)-secretase activity derived from the 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate-solubilized membrane fractions of HeLa cells, in an in vitro gamma-secretase assay.
View on PubMed
Total synthesis of ecteinascidin 743.
The total synthesis of ecteinascidin 743 (1), an extremely potent antitumor agent, has been accomplished. The synthesis features Ugi's 4CC reaction, intramolecular Heck reaction, phenol-aldehyde…
View on PubMed
BIN1 regulates BACE1 intracellular trafficking and amyloid-β production.
TLDR
It is reported that the depletion of BIN1 increases cellular BACE1 levels through impaired endosomal trafficking and reduces Bace1 lysosomal degradation, resulting in increased Aβ production.
View on PubMed
Phenylpiperidine‐type γ‐secretase modulators target the transmembrane domain 1 of presenilin 1
TLDR
It is shown that a phenylpiperidine‐type compound GSM‐1 directly targets the transmembrane domain (TMD) 1 of presenilin 1 (PS1) by photoaffinity labelling experiments combined with limited digestion, indicating an allosteric action of G SM‐1 by directly binding to the TMD1 of PS1, pinpointing the target structure of the phenylmethine‐type GSMs.
View on Wiley
Divergent synthesis of multifunctional molecular probes to elucidate the enzyme specificity of dipeptidic gamma-secretase inhibitors.
TLDR
The divergent synthesis of molecular probes has been successfully applied to characterize the interaction of GSIs with their molecular targets and define the structural requirements for inhibitor binding to intramembrane-cleaving proteases.
View on PubMed
Allosteric regulation of γ-secretase activity by a phenylimidazole-type γ-secretase modulator
TLDR
A model for the mechanism of action of the phenylimidazole-type GSM in which binding at the luminal side of PS induces a conformational change in the catalytic center of γ-secretase to modulate Aβ production is provided.
View on Publisher
...
...
By clicking accept or continuing to use the site, you agree to the terms outlined in our Privacy Policy, Terms of Service, and Dataset License