Selective Catalysis with Peptide Dendrimers

Publisher Website
Google Scholar
Abstract
Peptide dendrimers incorporating 3,5-diaminobenzoic acid 1 as a branching unit (B) were prepared by solid-phase synthesis of ((Ac−A3)2B−A2)2B−Cys−A1−NH2 followed by disulfide bridge formation. Twenty-one homo- and heterodimeric dendrimers were obtained by permutations of aspartate, histidine, and serine at positions A1, A2, and A3. Two dendrimers catalyzed the hydrolysis of 7-hydroxy-N-methyl-quinolinium esters (2−5), and two other dendrimers catalyzed the hydrolysis of 8-hydroxy-pyrene-1,3,6-trisulfonate esters (10−12). Enzyme-like kinetics was observed in aqueous buffer pH 6.0 with multiple turnover, substrate binding (KM = 0.1−0.5 mM), rate acceleration (kcat/kuncat > 103), and chiral discrimination (E = 2.8 for 2-phenylpropionate ester 5). The role of individual amino acids in catalysis was investigated by amino acid exchanges, highlighting the key role of histidine as a catalytic residue, and the importance of electrostatic and hydrophobic interactions in modulating substrate binding. These experiments demonstrate for the first time selective catalysis in peptide dendrimers.