Cell-specific ligands comprising conjugates of saccharides and amino acids or peptides are synthesized from amino acids such as ornithine, lysine, peptides such as dilysine, diornithine or oligolysine and selected saccharides having reactive functional groups protected by appropriate blocking groups. Such glycopeptides include e.g. N2-N2, N6-bis[3-(a-D-mannopyranosylthio)propionyl]-L-lysyl} -N6- [3-(a-D-mannopyranosylthiolpropionyl]-L-lysine (5). Those compounds are useful as tissue specific substances, which when coupled with bioactive materials through metabolizable or hydrolyzable linkages, deliver such bioactive materials to the selected site. In this manner, antiinflammatory drugs such as dexamethasone are linked through a metabolizable or hydrolyzable linkage and on administration to an animal suffering from inflammatory disease carries the drug to the site of inflammation for intracellular release.
Cell-specific ligands for selective drug delivery to tissues and organs
作者:Mitree M. Ponpipom、Robert L. Bugianesi、James C. Robbins、T. W. Doebber、T. Y. Shen
DOI:10.1021/jm00144a004
日期:1981.12
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.
US4386026A
申请人:——
公开号:US4386026A
公开(公告)日:1983-05-31
Composition having anti-oxidant, anti-aging, and autophagy activities and uses thereof
申请人:Incospharm Corporation
公开号:US09920092B1
公开(公告)日:2018-03-20
Provided are a composition having anti-oxidant, anti-aging, and autophagy activities to thereby be useful for preventing, alleviating, or treating age-related metabolic diseases including neurodegenerative diseases or type 2 diabetes, and uses thereof.