Synthetic mimics of mammalian cell surface receptors: prosthetic molecules that augment living cells.
Specific receptors on the surface of mammalian cells actively internalize cell-impermeable ligands by receptor-mediated endocytosis. To mimic these internalizing receptors, my laboratory is studying artificial cell surface receptors that comprise N-alkyl derivatives of 3beta-cholesterylamine linked to motifs that bind cell-impermeable ligands. When added to living mammalian cells, these synthetic receptors insert into cellular plasma membranes, project ligand-binding small molecules or peptides from the cell surface, and enable living cells to internalize targeted proteins and other cell-impermeable compounds. These artificial receptors mimic their natural counterparts by rapidly cycling between plasma membranes and intracellular endosomes, associating with proposed cholesterol and sphingolipid-rich lipid raft membrane microdomains, and delivering ligands to late endosomes/lysosomes. This "synthetic receptor targeting" strategy is briefly reviewed here and contrasted with other related cellular delivery systems. Potential applications of artificial cell surface receptors as molecular probes, agents for cellular targeting, tools for drug delivery, and methods for ligand depletion are discussed. The construction of synthetic receptors as prosthetic molecules, designed to seamlessly augment the molecular machinery of living cells, represents an exciting new frontier in the fields of bioorganic chemistry and chemical biology.
Peterson
Blake R
BR
Department of Chemistry, Pennsylvania State University, 104 Chemistry Building, University Park, PA 16802, USA. brpeters@chem.psu.edu.
D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D018716:Molecular Mimicry; D015394:Molecular Structure; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000502:physiology; D013499:Surface Properties
D008024:Ligands; D011956:Receptors, Cell Surface; C034993:ganglioside receptor; C072855:cholesterylamine; D002784:Cholesterol