Abstract
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 A previously unpublished five-membered cyclic sulfonimidamide was also synthesized.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aspartic Acid / analogs & derivatives*
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Carboxypeptidases / antagonists & inhibitors
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Carboxypeptidases A
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HIV Protease Inhibitors / pharmacology
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Inhibitory Concentration 50
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Metalloendopeptidases / chemistry*
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Models, Chemical
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Pepsin A / antagonists & inhibitors
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Sulfonamides / chemistry*
Substances
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HIV Protease Inhibitors
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Sulfonamides
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Aspartic Acid
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Carboxypeptidases
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Carboxypeptidases A
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Pepsin A
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Metalloendopeptidases