title: High-affinity peptide nucleic acid oligomers containing tricyclic cytosine analogues.
abstract: [structure: see text] Peptide nucleic acid (PNA) monomers containing the tricyclic cytosine analogues phenoxazine, 9-(2-aminoethoxy)phenoxazine (G-clamp), and 9-(3-aminopropoxy)phenoxazine (propyl-G-clamp) have been synthesized. The modified nucleobases were incorporated into PNA oligomers using Boc-chemistry for solid-phase synthesis. PNAs containing single G-clamp modifications exhibit significantly enhanced affinity toward RNA and DNA targets relative to unmodified PNA while maintaining mismatch discrimination. These PNA G-clamp modifications exhibit the highest increase in affinity toward nucleic acid targets reported so far for PNA modifications.
authors.affiliation: Department of Medicinal Chemistry, Isis Pharmaceuticals, Inc., Carlsbad, California 92008, USA.
authors.forename: Kallanthottathil G
authors.initials: KG
authors.lastname: Rajeev
authors.forename: Martin A
authors.initials: MA
authors.lastname: Maier
authors.forename: Elena A
authors.initials: EA
authors.lastname: Lesnik
authors.forename: Muthiah
authors.initials: M
authors.lastname: Manoharan
mesh_terms: D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D010078:Oxazines / Q000737:chemistry; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D012313:RNA / Q000737:chemistry / Q000378:metabolism
chemical_list: C470812:9-(2-aminoethoxy)phenoxazine; C470813:9-(3-aminopropoxy)phenoxazine; D010078:Oxazines; D020135:Peptide Nucleic Acids; D012313:RNA; D003596:Cytosine; D004247:DNA; C039203:phenoxazine