Chemical modification of the α-amino group of ∈-guanidinated trypsin by carbamylation, thiocarbamylation, or amidination renders the enzyme inactive toward specific ester and amide substrates. The carbamylated enzyme retains weak reactivity toward the pseudosubstrates diisopropyl phosphorofluoridate and p-nitrophenyl-p′-guanidinobenzoate. The modified enzyme resembles in this regard trypsinogen and guanidinated trypsinogen which react with these pseudosubstrates four to six orders of magnitude more slowly than trypsin. Since the common chemical characteristic of these weakly reactive enzyme derivatives is a blocked α-amino group of Ile7, it follows that full enzymatic function requires that this group be free. It is proposed that during zymogen activation, inter alia, a latent enzymatic activity becomes very greatly enhanced rather than being generated de novo.
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