Esterolytic Peptide Dendrimers with a Hydrophobic Core and Catalytic Residues at the Surface

Abstract

(3S)-4-(9-Fluorenylmethoxycarbonylamino)-3-methyl(allyloxycarbonyl)aminoethyloxyacetic acid (1) was prepared from (R)-3-aminopropane-1,2-diol and used as branching unit for the synthesis of second generation peptide dendrimers with six individually addressable variable amino acid positions. Three pairs of diastereomeric dendrimers were prepared bearing a common hydrophobic core and permutations of the catalytic triad amino acids aspartate, histidine and serine at the surface. Dendrimers with two surface histidine residues catalyzed the hydrolysis of fluorogenic 8-acyloxypyrene-1,3,6-trisulfonates in aqueous buffer pH 6.0 with rate enhancement k cat /k uncat in the 10 3 range and Michaelis-Menten constants K M in the 10 À 4 M range. Substrate recognition involves electrostatic interactions, as shown by competitive inhibition of catalysis observed with pyrene-1,3,6,8-tetrasulfonate. The 4-fold to 7-fold lowering in K M between the butyryl and nonanoyl esters in the most active dendrimers provides evidence for a hydrophobic component in substrate binding, which is absent in a closely related, less active diastereomeric peptide dendrimer.

Antifouling Activity of Simple Synthetic Diterpenoids against Larvae of the Barnacle Balanus albicostatus Pilsbry

“…Compound 4 was finally purified by silica gel column chromatography, and the monosubstituted product was converted to the epoxide (compound 5 ) by treatment with sodium ethoxide in THF. The synthesis of all the above compounds are shown in Scheme 1 and discussed below and all reactions are carried out according to the literature protocols [ 19 , 20 , 21 ].…”

Combinatorial synthesis, selection, and properties of esterase peptide dendrimers

“…Using an asymmetrically protected branching unit allowed for the definition of 6 individually addressable amino acid positions per dendrimer, corresponding to 12 variable positions in the disulfidebridged dimer. 8 Although this approach did deliver esterase-like dendrimers from a small 27-member library built around a hydrophobic core and containing catalytic residues on the surface, the synthesis was relatively long and cumbersome.…”

STM Vizualization of Thiol‐Containing Peptide Dendrimers on Au(111)

“…While dendrimers 1 and 2 contain only the catalytic triad amino acid histidine, serine and aspartate beside cysteine or cystine, dendrimer 3 is assembled around a hydrophobic core with leucine and phenylalanine surrounding the cysteine residue, and a periphery displaying the catalytic triad amino acids histidine, aspartate and serine. [16] Dendrimer 3 was prepared in the course of a mechanistic study on esterase dendrimers. [8] STM experiments were first performed in air using dendrimers 1 and 2.…”