Synthesis and Esterolytic Activity of Catalytic Peptide Dendrimers

✍ Scribed by David Lagnoux; Estelle Delort; Céline Douat-Casassus; Annamaria Esposito; Jean-Louis Reymond

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 222 KB
• Volume: 10
• Category: Article
• ISSN: 0947-6539
• DOI: 10.1002/chem.200305578

✦ Synopsis

Abstract

Peptide dendrimers were prepared by solid‐phase peptide synthesis. Monomeric dendrimers were first obtained by assembly of a hexapeptide sequence containing alternate standard α‐amino acids with diamino acids as branching units. The monomeric dendrimers were then dimerized by disulfide‐bridge formation at the core cysteine. The synthetic strategy is compatible with functional amino acids and different diamino acid branching units. Peptide dendrimers composed of the catalytic triad amino acids histidine, aspartate, and serine catalyzed the hydrolysis of N‐methylquinolinium salts when the histidine residues were placed at the outermost position. The dendrimer‐catalyzed hydrolysis of 7‐isobutyryl‐N‐methylquinolinium followed saturation kinetics with a rate constant of catalysis/rate constant without catalysis (k~cat~/k~uncat~) value of 3350 and a rate constant of catalysis/Michaelis constant (k~cat~/K~M~) value 350‐fold larger than the second‐order rate constant of the 4‐methylimidazole‐catalyzed reaction; this corresponds to a 40‐fold rate enhancement per histidine side chain. Catalysis can be attributed to the presence of histidine residues at the surface of the dendrimers.