Acyl group transfer by proteases forming acyl–enzyme intermediate: Kinetic model analysis

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Abstract
A kinetic model of peptide synthesis via transfer of the acyl moiety from activated derivatives of amino acids (S) to nucleophiles (N) catalyzed by proteases forming an acyl–enzyme intermediate has been analyzed. The kinetic model takes into account the subsequent enzymatic hydrolysis of synthesized peptide (P), and so the kinetic curve for this compound shows a maximum (denoted as pmax). Particular stress is placed on analyzing the effects of initial concentrations and of kinetic constants on the value of pmax. The analysis has demonstrated that at a given ratio of initial S and N concentrations, pmax is affected only by (i) the ratio of the second‐order rate constants for enzymatic hydrolysis of S and P(α) and (ii) the ratio of rate constants for an attack of the acyl–enzyme intermediate by the nucleophile and water (β). These conclusions apply regardless of the existence of linear inhibition by the components of the reaction mixture. Thus, the kinetically controlled maximum yield of peptide (pmax) can be calculated a priori from values of α and β that can be estimated experimentally or from reference data. Simple analytical expressions were obtained, allowing a fairly accurate prediction of pmax for a broad spectrum of S and N initial concentrations.
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