Homo-and hetero-bifunctional glycodendrimers ending with up to 16 fucoside and/or galactoside residues were synthesized in good yields using a convergent approach. The biologically active surface carbohydrate moieties were assembled in a single and efficient step using ''click chemistry''. The relative binding and cross-linking abilities of these glycodendrimers were evaluated by turbidimetric analyses using both PA-IL and PA-IIL lectins from Pseudomonas aeruginosa. Insoluble complexes were rapidly observed from the first and second generations as well as from the mixed glycodendrimer 32. This hetero-bifunctional glycodendrimer was also evaluated with PA-IL alone and showed potent cross-linking properties. These novel heterobifunctional glycodendrimers may therefore constitute strong antiadhesin properties.

Enzymelike kinetics were observed in the hydrolysis of 7‐hydroxy‐1‐methylquinolium esters 2 under the catalysis of three of a family of synthetic peptide dendrimers 1. Their synthesis was based on a symmetrical branching diamino acid (B), three variable amino acid positions (A1, A2, A3=His, Asp, Ser), and a disulfide bond dimerization strategy. All possible permutations of the catalytic triad of the amino acids aspartate, histidine, and serine at the variable positions gave a family of 21 peptide dendrimers.

Glycopeptide dendrimers have been prepared bearing four or eight identical glycoside moieties at their surface (beta-glucose, alpha-galactose, alpha-N-acetyl-galactose, or lactose), natural amino acids within the branches (Ser, Thr, His, Asp, Glu, Leu, Val, Phe), 2,3-diaminopropionic acid as the branching unit, and a cysteine residue at the core. These dendrimers have been used as drug-delivery devices for colchicine. Colchicine was attached to the dendrimers at the cysteine thiol group through a disulfide or thioether linkage. The biological activities of the glycopeptide dendrimer conjugates were evaluated in HeLa tumor cells and non-transformed mouse embryonic fibroblasts (MEFs). The concentrations of glycopeptide dendrimer drug conjugates required to achieve inhibition of cell proliferation by interference with the tubulin system were found to be higher (IC50 > 1 microM) compared to the required colchicine concentration. On the other hand, the glycopeptide dendrimer conjugates inhibited the proliferation of HeLa cells 20-100 times more effectively than the proliferation of MEFs. In comparison, non-glycosylated dendrimers and colchicine itself showed a selectivity of 10-fold or less for HeLa cells.

Peptide dendrimers were prepared by solid-phase peptide synthesis. Monomeric dendrimers were first obtained by assembly of a hexapeptide sequence containing alternate standard alpha-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.

Wie Enzyme katalysieren drei Dendrimere aus einer Familie synthetischer Peptid‐Dendrimere 1 die Hydrolyse des 7‐Hydroxy‐1‐methylchinonesters 2. Die Synthese dieser Katalysatoren erfolgte ausgehend von symmetrisch verzweigten Diaminosäuren (B) durch Umsetzung mit drei variierenden Aminosäuren (A1, A2, A3=His, Asp, Ser) und Dimerisierung zu einem Disulfid. Unter Ausschöpfung aller Kombinationsmöglichkeiten der drei verwendeten Aminosäuren Aspartat, Histidin und Serin erhält man Zugang zu einer Familie von 21 Peptid‐Dendrimeren.