Rate enhancement and enantioselectivity in ester hydrolysis catalysed by cyclodextrin-peptide hybrids

A pair of cyclodextrin-peptide hybrids (CD-peptides) having three functional groups, beta-cyclodextrin (beta-CD), imidazole and carboxylate, in this order and in the reverse order were designed and synthesized as hydrolytic catalysts. These CD-peptides were designed so as to make three functional groups placed on the same side of the alpha-helix peptide work together. Another pair of CD-peptide hybrids which lack the carboxylate were also designed and synthesized in order to examine the effect of the carboxylate in the novel catalysts. Circular dichroism studies revealed that these CD-peptides have stable alpha-helix structures and their alpha-helix contents were high enough (around 70%) to place the functional groups at appropriate positions in the CD-peptides. Boc-D-alanine p-nitrophenyl ester and Boc-L-alanine p-nitrophenyl ester were chosen as substrates and the enantioselectivity of the catalysts in the hydrolysis was examined. Kinetic studies suggested that the presence of carboxylate in the CD-peptides enhances the ester hydrolysis with substrate selectivity.