Sri International

Sequenom, Inc.

Daniel J Pollart

Christopher Hank Becker

Joseph Albert Monforte

Thomas Andrew Shaler

William W Lee

Edward W Grange

J Martin Brown

Abelardo P Martinez

Michael Tracy

Releasable tag reagents for use in the detection and analysis of target molecules, particular in mass spectrometric analyzes are provided. Also provided are methods of detection that employ releasable tag reagents.

Releasable nonvolatile mass-label molecules

Releasable tag reagents for use in the detection and analysis of target molecules, particular in mass spectrometric analyses are provided. Also provided are methods of detection that employ releasable tag reagents.

The present invention provides modified oligonucleotide primers designed to incorporate a cleavable moiety so that a 3' portion of the primer (linked to an extension product) can be released from an upstream 5&#x2032; portion of the primer. Upon selective cleavage of the cleavable site, primer extension products that contain about five or fewer base pairs of the primer sequence are released, to provide more useful sizing and sequence information per fragment than extension products containing the entire primer.

Primers useful for sizing nucleic acids

A method of using 1,2,4-benzotriazine oxides, some of which are novel compounds, as radiosensitizers and selective cytotoxic agents is disclosed. These compounds are shown to specifically radiosensitize hypoxic tumor cells. Some are additionally disclosed to be useful as specific cytotoxic agents for these cells. They also show an unexpected ability to radiosensitize aerobic cells following or preceding a hypoxic incubation of the cells with the drug. This provides a basis for selective radiosensitization of tumors compared to normal cells. A novel method for preparing the 1,2,4-benzotriazine oxides is also disclosed.

1,2,4-Benzotriazine oxides as radiosensitizers and selective cytotoxic agents

Using nonvolatile, releasable, mass-labels, the present invention provides for the synthesis and use of mass-labeled compounds to specifically interact with biomolecular targets. Following binding of the mass-labeled compounds to the target molecule, the unique mass-label can be analyzed using mass spectrometry to identify and characterize the target molecule. In one embodiment of the invention, a mass-labeled oligonucleotide probe is used to identify a specific gene sequence. A myriad of mass-labeled compounds may be produced for use in a wide variety of interactions such as oligonucleotide-oligonucleotide hybridization, polynucleotide-polynucleotide interactions, enzyme-substrate or substrate analog/intermediate interactions, polypeptide-nucleic acid interactions, protein-ligand interactions, receptor-ligand interactions, polypeptide-metal interactions, nucleic acid-metal interactions or antigen-antibody interactions. Also contemplated are combinatorial processes for creating large libraries of compounds permitting rapid screening for a wide variety of targets.

Releasable nonvolatile mass label molecules

A method of using 1,2,4-benzotriazine oxides, some of which are novel compounds, as radiosensitizers and selective cytotoxic agents is disclosed. These compounds are shown to specifically radiosensitive hypoxic tumor cells. Some are additionally disclosed to be useful as specific cytotoxic agents for these cells. They also show an unexpected ability to radiosensitize aerobic cells following or preceding a hypoxic incubation of the cells with the drug. This provides a basis for selective radiosensitization of tumors compared to normal cells. A novel method for preparing the 1,2,4-benzotriazine oxides is also disclosed.

1, 2, 4-benzotriazine oxides as radiosensitizers and selective cytotoxic agents

1,2,4-benzotriazine oxides as radiosensitizers and selective cytotoxic

The present invention provides modified oligonucleotide primers designed to incorporate a cleavable moiety so that a 3' portion of the primer (linked to an extension product) can be released from an upstream 5' portion of the primer. Upon selective cleavage of the cleavable site, primer extension products that contain about five or fewer base pairs of the primer sequence are released, to provide more useful sizing and sequence information per fragment than extension products containing the entire primer.

Oligonucleotide sizing using cleavable primers

The present invention provides modified oligonucleotide primers that (i) are designed for attachment to a solid support in a manner that does not block the ability to extend the primer from its 3' end, and (ii) incorporate a clearable moiety so that a 3' portion of the primer (linked to an extension product) can be released from an immobilized 5' portion. Upon selective cleavage of the cleavable site, a large portion of the primer fragment remains affixed to the solid support. This enables the release of primer extension products that contain about five or fewer base pairs of the primer sequence, to provide more useful sizing and sequence information per fragment than extension products containing the entire primer.

Oligonucleotide sizing using immobilized cleavable primers

A method of using 1,2,4-benzotriazine oxides, some of which are novel compounds, as radiosentitizers and selective cytotoxic agents is disclosed. These compounds are shown to specifically radiosensitize hypoxic tumor cells. Some are additionally disclosed to be useful as specific cytotoxic agents for these cells. They also show an unexpected ability to radiosensitize aerobic cells following or preceding a hypoxic incubation of the cells with the drug. This provides a basis for selective radiosensitization of tumors compared to normal cells. A novel method for preparing the 1,2,4- benzotriazine oxides is also disclosed.

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Menlo Park, CA, United States of America

Daniel J Pollart