Quantitative structure activity relationships in the synthesis of AcXYNH2 dipeptides by α-chymotrypsin in reversed micelles

Chemical synthesis and crystallization of the dipeptide AcPheIleNH2 in TTAB/heptane/octanol reversed micelles

“…The substrate ester not converted to dipeptide (13%) was directed towards the formation of the hydrolysis (10%) and transesterification side-products (3%). The reaction rates are four orders of magnitude lower than those reported in the literature for the α-chymotrypsin catalyzed synthesis in an equivalent reversed micellar system [17]. The dipeptide could also be synthesized at lower (4 and 10 • C) and higher (37 • C) temperatures, but with lower yields (<60%).…”

“…These conditions had been previously optimized for the enzymatic synthesis of AcPheIleNH 2 [17]. All concentrations are reported to the total volume of the system with exception of buffer molarity which is referred to the volume of the aqueous pool.…”

“…However, given the large free energy difference between hydrolyzed and condensed amino acids, equilibrium is mostly shifted towards hydrolysis. Thus, reversed micelles, with their characteristic low water content (typically <5 M), provide favorable thermodynamic conditions for the enzymatic formation of peptide bonds [15][16][17].…”

“…Another important characteristic Scheme 1. of this system is the low solubility of the dipeptide in the reaction media. The concomitant crystallization during the reaction, together with the low water content of the media, thus favors the synthesis of the dipeptide by shifting the equilibrium towards the product side [17].…”