Synthesis of dipeptides by suspension-to-suspension conversion via thermolysin catalysis: from analytical to preparative scale.
When using proteases in direct reversal of their normal hydrolytic function, the equilibrium position is very important in limiting the attainable yield in equilibrium-controlled enzymic peptide synthesis. Analysis of the equilibrium position reveals a favourable shift towards the peptide product if starting materials are largely undissolved in the reaction medium and the product precipitates. This approach enabled us to obtain high peptide yields in thermolysin-catalysed reactions in high-density aqueous media with an equimolar supply of substrates. The easy scale-up (up to mol-scale) of this approach is demonstrated by two examples. Z-His-Phe-NH2 and Z-Asp-Phe-OMe, precursors for cyclo-[-His-Phe-] and the low-calorie sweetener Aspartame, respectively, were synthesized in preparative yields of 84-88%.
Eichhorn
U
U
Degussa AG, ZN Wolfgang, Hanau, Germany.
Bommarius
A S
AS
Drauz
K
K
Jakubke
H D
HD
D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D004151:Dipeptides / Q000138:chemical synthesis*; D013820:Thermolysin / Q000737:chemistry*
D004151:Dipeptides; D013820:Thermolysin