This chapter discusses the strategies for characterizing, cloning, and expressing soluble endopeptidases. The cloning of the complementary DNA encoding an endopeptidase becomes a crucial step in explicating the role that the peptidase plays in nervous system function. Ultimately, elucidating the function and structure of one such protease can aid in understanding the regulation of neuropeptide function by these enzymes as a class. The peptidases can be targeted for pharmacological intervention through the use of specifically designed modulatory ligands, either agonistic or antagonistic. Examples using this rationale involve the development of inhibitors of the human immunodeficiency virus aspartic protease as a treatment for human immunodeficiency virus, inhibitors of angiotensin-converting enzyme, such as captopril, to treat hypertension, and inhibitors of enkephalinase as a treatment for congestive heart failure and as a nonaddictive analgesic.
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