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

A pair of cyclodextrin-peptide hybrids (CD-peptides) having three functiona l groups, beta-cyclodextrin (beta-CD), imidazole and carboxylate, in this o rder and in the reverse order were designed and synthesized as hydrolytic c atalysts. These CD-peptides were designed so as to make three functional gr oups placed on the same side of the alpha-helix peptide work together. Anot her pair of CD-peptide hybrids which lack the carboxylate were also designe d 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 hig h enough (around 70%) to place the functional groups at appropriate positio ns 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 th at the presence of carboxylate in the CD-peptides enhances the ester hydrol ysis with substrate selectivity.