Cell-specific ligands for selective drug delivery to tissues and organs

Abstract

Various numbers of D-mannose residues have been attached via spacer arms to lysine, dilysine, and oligolysine backbones. These D-mannosyl peptide analogues were found to be potent competitive inhibitors of the uptake of 125I-labeled D-mannose-bovine serum albumin conjugate by rat alveolar macrophages. The inhibitory potency of these synthetic ligands increased with increasing number of carbohydrate moieties. The chirality of the peptide backbone did not appear to play a major role in binding, whereas variations of the length and linkage of the spacer arm notably affected the inhibitory activities. The saccharide specificity of the macrophage receptor was demonstrated by the inactivity of the corresponding D-galactosyl peptide analogues. The L-fucosyl peptide derivative was only weakly active. The trimannosyldilysine ligand (KI = 3.9 microM) and its analogues are potentially useful in selective delivery of therapeutic agents to macrophages.

Novel Hyperbranched Glycomimetics Recognized by the Human Mannose Receptor: Quinic or Shikimic Acid Derivatives as Mannose Bioisosteres

“…The observed differences might originate from divergences in the fine structure of the mannoside and glycoside trees. Indeed, the nature, size, and shape of such multivalent ligands can deeply influence their interaction with receptors as previously mentioned 13a, 13c, 28. presently mannoside and glycoside clusters have been elaborated on the same lysinyl cores but these mainly differ in their branching pattern and their overall charge at physiological pH values (neutral or negative).…”

Investigations on biodistribution of technetium-99m-labeled carbohydrate-coated poly(propylene imine) dendrimers

“…Multiantenary systems bind to lectin receptors with more efficiency because the high density of carbohydrates present at their surface increases the probability of lectin-carbohydrate interaction and strength of association-a phenomenon called the cluster effect [39]. That the carbohydrate-lectin interaction depends on the density of the interacting partners has stimulated many workers to synthesize and evaluate multiantenary systems [40][41][42]. Glycodendrimers are ideally suited for the cluster effect [18], which could be a mechanism involved in larger and longer retention of M-PPI and L-PPI in liver.…”

Mannosylated self-assembled structures for molecular confinement and gene delivery applications

“…Bis-mannosylated lysine (3) was prepared by a slightly modified previously reported procedure [16,17] via Scheme 1 [18]. Sample Preparation for different microscopy analysis, i.e., AFM, TEM, SEM, fluorescence microscopy, and optical microscopy, was done by dissolving 1 mM of 3 in deionized water for 16 h at 37°C.…”