Molecular umbrella-assisted transport of an oligonucleotide across cholesterol-rich phospholipid bilayers.
A series of molecular umbrella conjugates, derived from cholic acid, deoxycholic acid, spermidine, lysine, and 5-mercapto-2-nitrobenzoic acid, have been synthesized and found capable of transporting an attached 16-mer oligonucleotide (S-dT16) across liposomal membranes made from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyldglycerol (POPG), and cholesterol [POPC/POPG/cholesterol (65/5/30; mol/mol/mol, v/v/v)] at 37 degrees C. Those molecular umbrellas containing four choloyl (or deoxycholoyl) groups resulted in significantly faster rates of transport as compared to those containing only two such moieties. A model that accounts for these membrane transport processes is proposed.
Janout
Vaclav
V
Department of Chemistry, Lehigh University, Bethlehem, Pennsylvania 18015, USA.
Jing
Bingwen
B
Regen
Steven L
SL
D001692:Biological Transport; D002784:Cholesterol / Q000737:chemistry*; D019826:Cholic Acid / Q000737:chemistry; D003840:Deoxycholic Acid / Q000737:chemistry; D008051:Lipid Bilayers / Q000138:chemical synthesis / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D008239:Lysine / Q000737:chemistry; D008958:Models, Molecular; D009579:Nitrobenzoates / Q000737:chemistry; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D013095:Spermidine / Q000737:chemistry; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds
D008051:Lipid Bilayers; D008081:Liposomes; D009579:Nitrobenzoates; D009841:Oligonucleotides; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D010743:Phospholipids; D013438:Sulfhydryl Compounds; D003840:Deoxycholic Acid; C011136:thionitrobenzoic acid; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; D002784:Cholesterol; D019826:Cholic Acid; D008239:Lysine; C028694:1-palmitoyl-2-oleoylphosphatidylcholine; D013095:Spermidine