2. Academic Validation
  3. A novel strategy for designing irreversible inhibitors of metalloproteases: acetals as latent electrophiles that interact with catalytic nucleophile at the active site

A novel strategy for designing irreversible inhibitors of metalloproteases: acetals as latent electrophiles that interact with catalytic nucleophile at the active site

  • Org Lett. 2000 Oct 5;2(20):3149-52. doi: 10.1021/ol006346w.
M S Han 1,  C H Ryu,  S J Chung,  D H Kim
Affiliations

Affiliation

  • 1 Center for Biofunctional Molecules and Department of Chemistry, Pohang University of Science and Technology, San 31 Hyojadong, Pohang 790-784, Korea.
PMID: 11009368 DOI: 10.1021/ol006346w
Abstract

A new strategy for design of irreversible inactivators for Carboxypeptidase A (CPA), a prototypic zinc protease, has been developed by exploiting the property of acetals to generate an oxacarbenium ion intermediate in the conversion into the corresponding carbonyl compounds. The design strategy is exemplified by 2-benzyl-5-alkyl-3,5-dioxapentanoic acids (1a-c). Interestingly, (R)-1b is slightly more potent than an (S)-1b as an inactivator of CPA.

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