Reactivity of easily removable protecting groups for glycine in peptide synthesis using papain as catalyst

Abstract

The reactivity of enzymatically removable protecting groups in peptide synthesis (phenyl acetyl and mandelyl) has been studied for the papain-catalyzed condensation between different n-α protected esters of glycine and H-Trp-OBzl. These protecting groups have also been compared with Z and Boc usually employed in chemical and enzymatic peptide synthesis. PhAc-Gly-OCam and Mand-Gly-OBzl gave good yields (89–90%) using papain deposited onto celite in saturated ethyl acetate and with 0.2% (v/v) of buffer content, respectively. The above acyl donors gave similar synthetic yields than Z-Gly-OCam and higher than Boc-Gly-OCam derivatives. All these enzymatic synthesis reactions have been performed with the nucleophile as limiting reagent. In all cases, the final yields were influenced by secondary reactions of the dipeptide product leading to its hydrolysis or additional H-Trp-OBzl condensation; thus, it has been necessary to determine the reaction conditions which minimize the undesired by-products.