Role of peptide substrate structure in the selective processing of peptide prohormones at basic amino acid pairs by endoproteases

Abstract
Three putative processing enzymes, each with defined action in a prohormone system, a ‘pro‐ocytocin‐neurophysin convertase’ from bovine neurohypophysis secretory granules, a ‘Leu‐enkephalin Arg6 generating enzyme’ from human CSF and the endoprotease from the ‘S‐28 convertase’ complex of rat brain cortex, were tested for their ability to hydrolyze peptides deriving from pro‐ocytocin, pro‐enkephalin B and pro‐somatostatin, respectively at pairs of basic amino acids. The observations suggest that structural parameters specified by the peptide region around the dibasic moieties govern recognition by the enzyme and define which peptide bond is hydrolyzed.

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