Biomaterial Database

Phosphorothioate oligonucleotides: chemistry, purification, analysis, scale-up and future directions. 1991

G Zon, and T G Geiser

Applied Biosystems, Inc., Therapeutics Group, Foster City, CA 94404.

There is widespread and growing interest in the use of phosphorothioate-modified oligonucleotides as sequence-specific agents to control transcription, splicing, translation and other regulated processes in vitro and in vivo, as pharmaceuticals. These exciting applications are predicated on the resistance of phosphorothioate oligonucleotides to degradation by nucleases, a property that results simply from incorporation of sulfur into the phosphate backbone. The popularity of phosphorothioate oligonucleotide analogs derives from several of their features: relatively easy automated synthesis, uncomplicated purification and handling, plus high solubility in water. Presented here are current preparative and analytical methods, together with a comprehensive comparative analysis of solid-phase and solution processes for manufacturing phosphorothioate oligonucleotides as bulk pharmaceutical compounds for clinical evaluation. A prospective view of the future is offered with the hope of directing attention to important areas of needed research dealing with phosphorothioate oligonucleotide technology in particular, and manufacturing of nucleic acid pharmaceuticals in general.

UI	MeSH Term	Description	Entries
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009841	Oligonucleotides	Polymers made up of a few (2-20) nucleotides. In molecular genetics, they refer to a short sequence synthesized to match a region where a mutation is known to occur, and then used as a probe (OLIGONUCLEOTIDE PROBES). (Dorland, 28th ed)	Oligonucleotide
D005544	Forecasting	The prediction or projection of the nature of future problems or existing conditions based upon the extrapolation or interpretation of existing scientific data or by the application of scientific methodology.	Futurology,Projections and Predictions,Future,Predictions and Projections
D001483	Base Sequence	The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.	DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D013873	Thionucleotides	Nucleotides in which the base moiety is substituted with one or more sulfur atoms.
D015394	Molecular Structure	The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.	Structure, Molecular,Molecular Structures,Structures, Molecular