| Title : Divergent synthesis of multifunctional molecular probes to elucidate the enzyme specificity of dipeptidic gamma-secretase inhibitors - Fuwa_2007_ACS.Chem.Biol_2_408 |
| Author(s) : Fuwa H , Takahashi Y , Konno Y , Watanabe N , Miyashita H , Sasaki M , Natsugari H , Kan T , Fukuyama T , Tomita T , Iwatsubo T |
| Ref : ACS Chemical Biology , 2 :408 , 2007 |
|
Abstract :
Divergent synthesis of multifunctional molecular probes based on caprolactam-derived dipeptidic gamma-secretase inhibitors (GSIs), Compound E (CE) and LY411575 analogue (DBZ), was efficiently accomplished by means of Cu(I)-catalyzed azide/alkyne fusion reaction. Photoaffinity labeling experiments using these derivatives coupled to photoactivatable and biotin moieties provided direct evidence that the molecular targets of CE and DBZ are the N-terminal fragment of presenilin 1 within the gamma-secretase complex. Moreover, these photoprobes directly targeted signal peptide peptidase. These data suggest that 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. |
| PubMedSearch : Fuwa_2007_ACS.Chem.Biol_2_408 |
| PubMedID: 17530731 |
Fuwa H, Takahashi Y, Konno Y, Watanabe N, Miyashita H, Sasaki M, Natsugari H, Kan T, Fukuyama T, Tomita T, Iwatsubo T (2007)
Divergent synthesis of multifunctional molecular probes to elucidate the enzyme specificity of dipeptidic gamma-secretase inhibitors
ACS Chemical Biology
2 :408
Fuwa H, Takahashi Y, Konno Y, Watanabe N, Miyashita H, Sasaki M, Natsugari H, Kan T, Fukuyama T, Tomita T, Iwatsubo T (2007)
ACS Chemical Biology
2 :408