Glycosylation of the primary binding pocket of a subtilisin protease causes a remarkable broadening in stereospecificity in peptide synthesis

Abstract

Site-selective glycosylation at position 166 at the base of the primary specificity S₁ pocket in the serine protease subtilisin Bacillus lentus (SBL) created glycoproteins that are capable of catalyzing the coupling reactions of not only L- amino acid esters but also D-amino acid esters to give the corresponding dipeptides in good yields as a result of greatly broadened substrate specificities that can be rationalized by the interaction of the glycans acting as chiral auxiliaries in stereochemically mismatched pairs.