Efficient synthesis of oligonucleotide conjugates on solid-support using an (aminoethoxycarbonyl)aminohexyl group for 5′-terminal modification

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 8, 2009, Pages 2144-2147

  Kojima, Naoshi ^a   Takebayashi, Toshie ^a   Mikami, Akiko ^a   Ohtsuka, Eiko ^a   Komatsu, Yasuo ^a  

^a NATIONAL INSTITUTE OF ADVANCED INDUSTRIAL SCIENCE AND TECHNOLOGY AIST   (Japan)

Author keywords

Amino linker; Conjugation; Oligonucleotide; Solid phase synthesis

Indexed keywords

(AMINOETHOXYCARBONYL)AMINOHEXYL; ALIPHATIC COMPOUND; AMINE; AMINO ACID; CARBONYL DERIVATIVE; CHOLESTEROL; FUNCTIONAL GROUP; OLIGONUCLEOTIDE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL MODIFICATION; CONJUGATE; CONJUGATION; QUANTUM YIELD; SOLID; SYNTHESIS;

AMINO ACID MOTIFS; CHEMISTRY, PHARMACEUTICAL; GLYCINE; OLIGONUCLEOTIDES;

EID: 63149198944     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.02.121     Document Type: Article

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16. The 5′-amino-modified ONTs on the CPG-support (0.1 μmol) were treated with N-Fmoc-Phe (10 equiv), the coupling reagent (10 equiv) and DIEA (20 equiv) in DMF (0.5 mL), or N-Fmoc-Phe-OPfp ester (10 equiv) and DIEA (20 equiv) in DMF (0.5 mL). See the Supplementary data for more details.
17. The products were confirmed by MALDI-TOF/MS measurements. See the Supplementary data.
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20. The 5′-amino-modified ONTs on the CPG-support (0.1 μmol) were treated with cholesteryl chloroformate (40 equiv) and DIEA (80 equiv for X-T15, 20 equiv for X-25) in dichloromethane (0.5 mL) at room temperature for 15 min. See the Supplementary data for more details. The longer ONTs were used in the cholesterol coupling reactions for the purpose of increasing the solubility of the chol-ONT conjugates in water.
21. The 5′-amino-modified ONTs on the CPG-support (0.1 μmol) were treated with cholesteryl chloroformate (40 equiv), DMAP (20 equiv) and DIEA (20 equiv) in dichloromethane (0.5 mL) at room temperature for 15 min. See the Supplementary data for details.
22. The 5′-amino-modified ONT on the CPG-support (0.1 μmol) was treated with cholesteryl chloroformate (150 equiv), DMAP (20 equiv) and DIEA (20 equiv) in dichloromethane (0.5 mL) at room temperature for 5 min. See the Supplementary data for details.