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

Publisher Website
Google Scholar
Abstract
Various numbers of D-mannose residues were attached via spacer arms to lysine, dilysine and oligolysine backbones. These D-mannosyl peptide analogs were 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; 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 analogs. The L-fucosyl peptide derivative was only weakly active. The trimannosyldilysine ligand (KI [inhibition constant] = 3.9 .mu.M) and its analogs are potentially useful in selective delivery of therapeutic agents to macrophages.