title: The Medicinal Chemistry of Therapeutic Oligonucleotides.
abstract: Oligonucleotide-based therapeutics have made rapid progress in the clinic for treatment of a variety of disease indications. Unmodified oligonucleotides are polyanionic macromolecules with poor drug-like properties. Over the past two decades, medicinal chemists have identified a number of chemical modification and conjugation strategies which can improve the nuclease stability, RNA-binding affinity, and pharmacokinetic properties of oligonucleotides for therapeutic applications. In this perspective, we present a summary of the most commonly used nucleobase, sugar and backbone modification, and conjugation strategies used in oligonucleotide medicinal chemistry.
authors.affiliation: Department of Medicinal Chemistry, Ionis Pharmaceuticals , 2855 Gazelle Court, Carlsbad, California 92010, United States.
authors.forename: W Brad
authors.initials: WB
authors.lastname: Wan
authors.affiliation: Department of Medicinal Chemistry, Ionis Pharmaceuticals , 2855 Gazelle Court, Carlsbad, California 92010, United States.
authors.forename: Punit P
authors.initials: PP
authors.lastname: Seth
mesh_terms: D002626:Chemistry, Pharmaceutical; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D009841:Oligonucleotides