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Aza-peptide epoxides, a new class of irreversible protease inhibitors, are specific for the clan CD cysteine proteases. The inhibitors have second-order rate constants up to 10(5) M(-1) s(-1), with the most potent epoxides having the S,S stereochemistry. The aza-Asn derivatives are effective legumain inhibitors, while the aza-Asp epoxides were specific for caspases. The inhibitors have little or no inhibition with other proteases such as chymotrypsin, papain, or cathepsin B.

The pivotal role of receptor tyrosine kinases (RTKs) in regulation of cellular growth and differentiation has triggered considerable interest in the identification of novel members of this ubiquitous protein family. Screening techniques, which were not dependent on function, brought about the isolation of numerous novel RTKs for which the ligands were not known. Many were EPH-like RTKs, which comprise the largest RTK family known to date (1-19).In contrast to the PCR-based approaches used for most other EPH-like RTKs, human EPH-like kinase (HEK) was identified on the cell surface of a human pre-B-cell line with monoclonal antibody (mAb) IIIA4 (2). HEK protein was affinity purified on a mAb IIIA4 column (2), and its amino acid sequence revealed homology with EPH and the predicted amino acid sequences of other EPH-like RTKs [ELK (3), ECK (4), and ERK (5)]. The sequences of the mouse (MEK4) and chicken (CEK4) homologues of HEK have also been reported (6, 7). To date, at least 28 members of the EPH subfamily have been identified in diverse vertebrate species including zeThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.