Method of expanded porphyrin-oligonucleotide conjugate synthesis
AssigneesPharmacyclics, Inc., Board of Regents, Univ. of Texas Sys.
InventorsDarren Magda, Jonathan L. Sessler, Brent L. Iverson, Petra I. Sansom, Shaun P. Crofts
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Abstract
The invention is directed to a method of incorporating expanded porphyrins, and particularly of incorporating a sapphyrin or a texaphyrin, before, during, or after chemical synthesis of an oligomer to form an expanded porphyrin-oligonucleotide conjugate, and particularly a sapphyrin- or texaphyrin-oligonucleotide conjugate. This method includes reacting derivatized nucleotides and a sapphyrin or a texaphyrin in a desired order in an automated or manual DNA synthesizer having a solid support to form a sapphyrin- or a texaphyrin-oligonucleotide conjugate.
Claims29
A method of synthesizing an expanded porphyrin-nucleotide conjugate in a DNA synthesizer, the method comprising reacting an expanded porphyrin with a nucleotide using the DNA synthesizer, to form an expanded porphyrin-nucleotide conjugate.
A method of obtaining a 3'-linked expanded porphyrin-nucleotide conjugate, the method comprising the steps of:
- attaching an expanded porphyrin to a solid support of a DNA synthesizer;
- attaching a nucleic acid residue to the expanded porphyrin, followed by the attachment of one or more additional nucleic acid residues in stepwise synthesis to obtain a desired oligonucleotide;
- cleaving the resulting 3'-linked expanded porphyrin-nucleotide conjugate from the solid support;
- and deprotecting the oligonucleotide.
A method of obtaining a 5'-linked expanded porphyrin-nucleotide conjugate, the method comprising the steps of:
- attaching one or more nucleic acid residues to a solid support of a DNA synthesizer in stepwise synthesis to obtain a desired oligonucleotide;
- attaching an expanded porphyrin to the oligonucleotide as the final residue;
- cleaving the resulting 5'-linked expanded porphyrin-nucleotide conjugate from the solid support;
- and deprotecting the oligonucleotide.
A method of synthesizing a texaphyrin-nucleotide conjugate in a DNA synthesizer, the method comprising reacting a texaphyrin with a nucleotide using the DNA synthesizer, to form a texaphyrin-nucleotide conjugate.
Dependencies are inferred from the claim text.