Selective catalysis with peptide dendrimers.
Peptide dendrimers incorporating 3,5-diaminobenzoic acid 1 as a branching unit (B) were prepared by solid-phase synthesis of ((Ac-A(3))(2)B-A(2))(2)B-Cys-A(1)-NH(2) followed by disulfide bridge formation. Twenty-one homo- and heterodimeric dendrimers were obtained by permutations of aspartate, histidine, and serine at positions A(1), A(2), and A(3). 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 (K(M) = 0.1-0.5 mM), rate acceleration (k(cat)/k(uncat) > 10(3)), 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.
Douat-Casassus
Céline
C
Department of Chemistry & Biochemistry, University of Berne, Freiestrasse 3, CH-3012 Berne, Switzerland.
Darbre
Tamis
T
Reymond
Jean-Louis
JL
D000596:Amino Acids / Q000737:chemistry; D062365:Aminobenzoates / Q000737:chemistry; D001665:Binding Sites; D002384:Catalysis; D004952:Esters / Q000737:chemistry; D006639:Histidine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008956:Models, Chemical; D010455:Peptides / Q000138:chemical synthesis* / Q000378:metabolism; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism; D011806:Quinolinium Compounds / Q000737:chemistry; D055672:Static Electricity; D013379:Substrate Specificity
D000596:Amino Acids; D062365:Aminobenzoates; D004952:Esters; D010455:Peptides; D011108:Polymers; D011806:Quinolinium Compounds; C017856:3,5-diaminobenzoic acid; D006639:Histidine