Base modified nucleosides

C - Chemistry – Metallurgy – 07 – H

Patent

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260/210, 195/1.1

C07H 21/00 (2006.01) C07H 19/06 (2006.01) C07H 19/10 (2006.01) C07H 23/00 (2006.01)

Patent

CA 2021006

ABSTRACT OF THE DISCLOSURE The present invention relates to the preparation and isolation of 5-position modified uracil nucleosides and nucleotides and to their use in the synthesis of labeled oligonucleotides useful as nucleic acid probes. More specifically, the present invention provides for improved methods for the preparation of novel 5-aza uracil nucleoside derivatives wherein a 5-halo-uracil nucleoside is reacted with a bifunctional amine, such as diamine, a sulfhydrylamino compound, or an hydroxyamino compound, to yield the corresponding 5-(aza-aminoalkyl)uracil nucleoside, 5-(aza-sulfhydrylalkyl)uracil nucleoside or 5-(aza-hydroxyalkyl)uracil nucleoside, respectively, and for improved methods for the isolation of the products formed. These uracil nucleoside derivatives can be used as substrates in a method for preparing novel labeled oligonucleotides of DNA. Reporter groups can be attached either before or after the preparation of the oligonucleotides. These reporter group labeled oligonucleotides are especially useful when incorporated into nucleic acid probes which readily can be used in hybridization studies to form hybrids with either DNA or RNA. 06/3675z/46

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