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.