10.1021/jm0155695.s004
Jay S. Tung
Jay S.
Tung
David L. Davis
David L.
Davis
John P. Anderson
John
P. Anderson
Don E. Walker
Don E.
Walker
Shumeye Mamo
Shumeye
Mamo
Nancy Jewett
Nancy
Jewett
Roy K. Hom
Roy K.
Hom
Sukanto Sinha
Sukanto
Sinha
Eugene D. Thorsett
Eugene D.
Thorsett
Varghese John
Varghese
John
Design of Substrate-Based Inhibitors of
Human β-Secretase
American Chemical Society
2001
BACE
inhibitor 22
potency
2001-12-20 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Design_of_Substrate-Based_Inhibitors_of_Human_-Secretase/3680898
By use of the effectively cleaved <i>β</i>-secretase (BACE)
substrate (<b>1</b>), incorporation of a statine in P<sub>1</sub> resulted in a weak
inhibitor <b>13 </b>of the enzyme. Further substitution of P<sub>1</sub>‘-Asp by
P<sub>1</sub>‘-Val in <b>13</b> results in a potent inhibitor <b>22</b> of BACE. Removal
of the P<sub>10</sub>−P<sub>5</sub> residues on the N-terminal part of inhibitor <b>22</b>
resulted in no loss of potency (<b>23</b>). C-terminal truncations of
inhibitor <b>22</b> generally led to significant loss of potency.