title: Formation of the N(2)-acetyl-2,6-diaminopurine oligonucleotide impurity caused by acetyl capping.
abstract: The acetyl 'capping' reaction routinely employed during phosphorothioate oligonucleotide synthesis has been implicated in the formation of an impurity species with a mass 41 amu greater than the expected oligonucleotide molecule. The impurity has been found to arise by conversion of a protected guanine nucleobase to N(2)-acetyl-2,6-diaminopurine. A two-part mechanism is proposed consisting of transamidation of the protecting group on guanine and substitution of guanine's O(6) atom.
authors: Isis Pharmaceuticals, Inc., 2855 Gazelle Ct., Carlsbad, CA 92010, United States. Electronic address: arodrigu@isisph.com.
authors: Andrew A
authors: AA
authors: Rodriguez
authors: Isis Pharmaceuticals, Inc., 2855 Gazelle Ct., Carlsbad, CA 92010, United States.
authors: Isaiah
authors: I
authors: Cedillo
authors: Isis Pharmaceuticals, Inc., 2855 Gazelle Ct., Carlsbad, CA 92010, United States.
authors: Brendan P
authors: BP
authors: Mowery
authors: Isis Pharmaceuticals, Inc., 2855 Gazelle Ct., Carlsbad, CA 92010, United States.
authors: Hans J
authors: HJ
authors: Gaus
authors: Isis Pharmaceuticals, Inc., 2855 Gazelle Ct., Carlsbad, CA 92010, United States.
authors: Seetha S
authors: SS
authors: Krishnamoorthy
authors: Isis Pharmaceuticals, Inc., 2855 Gazelle Ct., Carlsbad, CA 92010, United States.
authors: Andrew K
authors: AK
authors: McPherson
mesh_terms: D015075:2-Aminopurine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D009841:Oligonucleotides; D015075:2-Aminopurine
keywords: Acetyl; Capping; Guanine; Guanosine; Impurity; Modification; Oligonucleotide; Solid-phase; Synthesis