Constrained peptidomimetics reveal detailed geometric requirements of covalent prolyl oligopeptidase inhibitors

…, L Juillerat-Jeanneret, N Moitessier

Index: Lawandi, Janice; Toumieux, Sylvestre; Seyer, Valentine; Campbell, Philip; Thielges, Sabine; Juillerat-Jeanneret, Lucienne; Moitessier, Nicolas Journal of Medicinal Chemistry, 2009 , vol. 52, # 21 p. 6672 - 6684

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Citation Number: 21

Abstract

Prolyl oligopeptidases cleave peptides on the carboxy side of internal proline residues and their inhibition has potential in the treatment of human brain disorders. Using our docking program fitted, we have designed a series of constrained covalent inhibitors, built from a series of bicyclic scaffolds, to study the optimal shape required for these small molecules. These structures bear nitrile functional groups that we predicted to covalently bind to the ...