ORGN 703 |
| Receptors on the surface of mammalian cells promote the uptake of cell-impermeable ligands by receptor-mediated endocytosis. To mimic this process, we synthesized small molecules designed to project protein-binding and drug-binding motifs from the surface of living mammalian cells. These synthetic receptors comprise N-alkyl derivatives of 3β-cholesterylamine as the plasma membrane anchor linked to 2,4-dinitrophenyl (DNP), 7-nitrobenz-2-oxa-1,3-diazole (NBD), D-Phe-D-Ala, and cyclic peptide headgroups that bind anti-dinitrophenyl IgG, vancomycin, and human IgG ligands. These nonnatural receptors mimic many natural receptors by avidly associating with cell surfaces (typical cellular t1/2~ 20 h), dynamically cycling between plasma membranes and intracellular endosomes (recycling t1/2 ~ 3 min), association with proposed lipid raft membrane microdomains, and delivery of cell-impermeable ligands to late endosomes/lysosomes. Synthetic cell surface receptors have potential applications as cellular probes, tools for drug delivery, and modulators of biological systems.
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Asymmetric Reactions, Molecular Recognition, Self Assembly, Bioorganic Chemistry, Process R&D
8:00 PM-10:00 PM, Wednesday, 16 March 2005 Convention Center -- Hall D, Poster
Division of Organic Chemistry |
