What question did this study set out to answer?

Identify and characterize novel small-molecule inhibitors of amyloid β-protein precursor γ-secretase to probe its catalytic mechanism and therapeutic potential in Alzheimer's disease.

July 6, 2000Biochemistry

L-685,458, an Aspartyl Protease Transition State Mimic, Is a Potent Inhibitor of Amyloid β-Protein Precursor γ-Secretase Activity

View Full Paper

Ask AI

Bookmark

Authors

MSMark S. ShearmanEditas Medicine (United States)DBDirk BeherAsceneuron (Switzerland)ECEarl E. ClarkeKing's College London

Discussion

Member takes

Implication

Biochemical study demonstrates potent inhibition of gamma-secretase activity by transition state mimic L-685,458, highlighting mechanisms for Alzheimer's disease therapeutics.

Key Points

Identify and characterize novel small-molecule inhibitors of amyloid β-protein precursor γ-secretase to probe its catalytic mechanism and therapeutic potential in Alzheimer's disease.
Assessed the inhibitory profile of the hydroxyethylene dipeptide isostere compound L-685,458 against amyloid β-protein precursor (AβPP) γ-secretase activity.
Evaluated the potency of inhibition across Aβ42 and Aβ40 peptide species and compared stereochemical selectivity requirements with HIV-1 aspartyl protease.
L-685,458 demonstrated potent inhibition of AβPP γ-secretase activity, showing comparable inhibitory strength against both Aβ42 and Aβ40 generation.
The compound functioned as an aspartyl protease transition state mimic, exhibiting a stereochemical configuration opposite to that required for HIV-1 protease inhibition to achieve target selectivity.

Cite This Study

Shearman et al. (2000) studied this question.

synapsesocial.com/papers/6a86c34e48ef9afcd2a23ced https://doi.org/10.1021/bi0005456

View Full Paper

Ask AI

Bookmark

Implication

Biochemical study demonstrates potent inhibition of gamma-secretase activity by transition state mimic L-685,458, highlighting mechanisms for Alzheimer's disease therapeutics.

L-685,458, an Aspartyl Protease Transition State Mimic, Is a Potent Inhibitor of Amyloid β-Protein Precursor γ-Secretase Activity

Discussion

Member takes

Implication

Key Points

Cite This Study

L-685,458, an Aspartyl Protease Transition State Mimic, Is a Potent Inhibitor of Amyloid β-Protein Precursor γ-Secretase Activity

Discussion

Member takes

Implication

Key Points

Cite This Study

Also Consider

Also Consider