Synthesis and properties of cholesteryl-modified triple-helix forming oligonucleotides containing a triglycyl linker.
In order to enhance the nuclear uptake of triple-helix forming oligonucleotides (TFOs), a triglycylcholesterol group was attached to the 3' end. The peptide unit was introduced as a "labile" linker with the aim of releasing the oligonucleotide from the endosomes by the action of peptidases after crossing the cell membrane. Cholesteryl-CPG (8) and -TentaGel (9) supports containing 2-[N-(glycylglycylglycyl)amino]propane-1,3-diol (GAP-3) linker were prepared and used for automated oligonucleotide synthesis. The synthesis, characterization, and stability of these compounds are described.
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Triplex Pharmaceutical Corporation, Woodlands, Texas 77380.
Hill
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Jayaraman
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D001483:Base Sequence; D002784:Cholesterol / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry*
D009841:Oligonucleotides; D009842:Oligopeptides; D002784:Cholesterol; C035647:glycyl-glycyl-glycine