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Incorporation of Sensitive Ester and Chloropurine Groups into Oligodeoxynucleotides through Solid‐Phase Synthesis
Author(s) -
Halami Bhaskar,
Shahsavari Shahien,
Nelson Zack,
Prehoda Lucas,
Eriyagama Dhananjani Nisansala Adikar Mudiyanselage,
Fang Shiyue
Publication year - 2018
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201801484
Subject(s) - chemistry , nucleophile , methoxide , potassium hydroxide , solid phase synthesis , ammonium hydroxide , anhydrous , cleavage (geology) , methanol , hydroxide , linker , combinatorial chemistry , organic chemistry , peptide , catalysis , biochemistry , fracture (geology) , computer science , engineering , operating system , geotechnical engineering
Nucleosides containing ester groups that are sensitive to nucleophiles were incorporated into oligodeoxynucleotides (ODNs) through solid phase chemical synthesis. The sensitive esters are located on a purine nucleobase. They are the esters of ethyl, 2‐methoxyethyl, 4‐methoxyphenyl and phenyl groups, and a thioester. These esters cannot survive the deprotection and cleavage conditions used in known ODN synthesis technologies, which involve strong nucleophiles such as ammonium hydroxide and potassium methoxide (potassium carbonate in anhydrous methanol). To incorporate these sensitive groups into ODNs, the Dmoc (i. e. dimethyl‐1,3‐dithian‐2‐ylmethoxycarbonyl) phosphoramidites and linker were used for solid phase synthesis, which allowed ODN deprotection and cleavage to be carried out under non‐nucleophilic oxidative conditions. Sixteen ODN sequences containing these groups were synthesized and characterized with MALDI MS. In addition, the synthesis and characterization of three ODNs containing a nucleophile sensitive 6‐chloropurine using the same strategy are described.