Fluorescent dye phosphoramidite labelling of oligonucleotides
摘要:
A 5-carboxyfluorescein (FAM) phosphoramidite reagent has been synthesized for use on automated DNA synthesizers, to prepare fluorescent dye labelled oligonucleotides. Oligonucleotides can be labelled at any site in a sequence and multiple labelled. The FAM dye can also be coupled to a polystyrene synthesis support to prepare 3' fluorescent labelled oligonucleotides.
The invention provides nucleic acid monomers with a 2′-modification that are useful for the incorporation of dyes or blocking groups. The monomers can be incorporated on the 3′-end of a dual labeled probe to inhibit PCR polymerase extension during PCR. The polymerase is inhibited from extending the probe at the 3′-hydroxyl group when the monomer is present; there is no need to add a chemical moiety to the 3′-hydroxyl or remove the 3′-hydroxyl. The monomers can also be incorporated internally or at the 5′-end of the oligonucleotide. A detectable label, such as a fluorescent or quenching dye, can be incorporated on the 2′-position of such monomers.
Disclosed are novel 4-amino-thieno[3,2-c]pyridine-7-carboxylic acid amides, and their pharmaceutically acceptable salts and esters, that are selective inhibitors of KDR and/or FGFR kinases. These compounds and their pharmaceutically acceptable salts are anti-proliferative agents useful in the treatment or control of solid tumors, in particular solid cancerous tumors of the breast, colon, lung and prostate. Also disclosed are pharmaceutical compositions containing these compounds and methods of treating cancer using these compounds.
Disclosed are novel 4-amino-thieno[3,2-c]pyridine-7-carboxylic acid amides, and their pharmaceutically acceptable salts and esters, that are selective inhibitors of KDR and/or FGFR kinases. These compounds and their pharmaceutically acceptable salts are anti-proliferative agents useful in the treatment or control of solid tumors, in particular solid cancerous tumors of the breast, colon, lung and prostate. Also disclosed are pharmaceutical compositions containing these compounds and methods of treating cancer using these compounds.