The sulfonimidamide as a novel transition state analog for aspartic acid and metallo proteases.
We have developed a novel strategy for the preparation of tetrahedral transition state analogs for aspartic acid and metallo-proteases based upon the sulfonimidamide functional group. Our best alpha-des-amino dipeptide analog binds at least 100-fold tighter than the corresponding ground state structure (i.e., amide). A previously unpublished five-membered cyclic sulfonimidamide was also synthesized.
Cathers
B E
BE
The Department of Medicinal Chemistry, The University of Kansas, Lawrence 66045, USA.
Schloss
J V
JV
D001224:Aspartic Acid / Q000031:analogs & derivatives*; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors; D043422:Carboxypeptidases A; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008666:Metalloendopeptidases / Q000737:chemistry*; D008956:Models, Chemical; D010434:Pepsin A / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000737:chemistry*
D017320:HIV Protease Inhibitors; D013449:Sulfonamides; D001224:Aspartic Acid; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D010434:Pepsin A; D008666:Metalloendopeptidases