title: Conceptual "Heat-Driven" approach to the synthesis of DNA oligonucleotides on microarrays.
abstract: The discovery of deoxyribonucleoside cyclic N-acylphosphoramidites, a novel class of phosphoramidite monomers for solid-phase oligonucleotide synthesis, has led to the development of a number of phosphate protecting groups that can be cleaved from DNA oligonucleotides under thermolytic neutral conditions. These include the 2-(N-formyl-N-methyl)aminoethyl, 4-oxopentyl, 3-(N-tert-butyl)carboxamido-1-propyl, 3-(2-pyridyl)-1-propyl, 2-[N-methyl-N-(2-pyridyl)]aminoethyl, and 4-methythiobutyl groups. When used for 5'-hydroxyl protection of nucleosides, the analogous 1-phenyl-2-[N-methyl-N-(2-pyridyl)]aminoethyloxycarbonyl group exhibited excellent thermolytic properties, which may permit an iterative "heat-driven" synthesis of DNA oligonucleotides on microarrays. In this regard, progress has been made toward the use of deoxyribonucleoside cyclic N-acylphosphoramidites in solid-phase oligonucleotide syntheses without nucleobase protection. Given that deoxyribonucleoside cyclic N-acylphosphoramidites produce oligonucleotides with heat-sensitive phosphate protecting groups, blocking the 5'-hydroxyl of these monomers with, for example, the thermolabile 1-phenyl-2-[N-methyl-N-(2-pyridyl)]aminoethyloxycarbonyl group may provide a convenient thermo-controlled method for the synthesis of oligonucleotides on microarrays.
authors.affiliation: Division of Therapeutic Proteins, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
authors.forename: A
authors.initials: A
authors.lastname: Grajkowski
authors.forename: J
authors.initials: J
authors.lastname: Cieślak
authors.forename: M K
authors.initials: MK
authors.lastname: Chmielewski
authors.forename: V
authors.initials: V
authors.lastname: Marchán
authors.forename: L R
authors.initials: LR
authors.lastname: Phillips
authors.forename: A
authors.initials: A
authors.lastname: Wilk
authors.forename: S L
authors.initials: SL
authors.lastname: Beaucage
mesh_terms: D003853:Deoxyribonucleosides / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D006358:Hot Temperature; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis*; D009943:Organophosphorus Compounds / Q000737:chemistry
chemical_list: D003853:Deoxyribonucleosides; D009838:Oligodeoxyribonucleotides; D009943:Organophosphorus Compounds; C434331:phosphoramidite