Neorx Corporation

Isis Pharmaceuticals, Inc.

Competitive Technologies, Inc.

University Patents, Inc.

Competitve Technologies, Inc.

Eric K Yau

Marvin H Caruthers

Wolfgang K-d Brill

John Nielsen

Michael Ma

Linda M Gustavson

Louis J Theodore

Sudhakar Kasina

John M Reno

Yun-Xi Ma

The present invention provides aromatic amine substituted metal chelating compounds, chelates and chelate-targeting moiety conjugates formed from the chelating compounds, and methods for making and using these compounds. Metals capable of being chelated by the chelating compounds include radionuclides, such as .sup.99m Tc and .sup.186188 Re.

Aromatic amine substituted bridged nitrogen and sulfur donor atom

Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin, as well as related compounds, are described. Articles of manufacture useful in pretargeting methods are also discussed.

Production of nitro-benzyl-dota via direct peptide cyclization

The present invention relates to new and useful nucleoside thiophosphoroamidites and polynucleotide phosphorodithioate compounds as well as the processes whereby these compounds may be used for synthesizing new mononucleotides and polynucleotides having phosphorothioate and phosphorodithioate internucleotide linkages.

Polynucleotide phosphorodithioate compounds

Nucleoside thiophosphoramidites

A process for preparing phosphorothioate oligonucleotides utilizes S-(alkaryl or aryl) phosphorothioate compounds as intermediates suitable for use in the solution phase. A dinucleotide is prepared from a nucleoside intermediate that has been phosphitylated with an S-(alkaryl or aryl) alkyl phosphorothioate diester salt. The alkyl ester group is removed and the resulting nucleotide diester is reacted with a further nucleoside having a free 5'-hydroxyl group. Nucleotide units are linked together to yield compounds of the structure: ##STR1## where X is H, a first blocking group, a nucleoside, a nucleotide or an oligonucleotide; Y is H, a second blocking group, a nucleoside, a nucleotide or an oligonucleotide; R is an alkaryl or aryl group; n is an integer greater than 0; and Bx is a heterocyclic base. Deblocking of the S-alkaryl or S-aryl moiety yields a phosphorothioate oligonucleotide.

Process for preparing phosphorothioate oligonucleotides

Dinucleoside phosphorodithioate phosphoramidite precursors useful in the synthesis of oligonucleotide phosphorodithioate which can be used as antisense inhibitors of translation.

Pretargeting methods and compounds

The present invention relates to new and useful nucleside thiophosphoramidite, polynucleotide dithioate phosphoramidite and polynucleotide phosphorothioamidate phosphoramidite compounds as well as the process whereby these compounds can be used for synthesizing new monoucleotides and polynucleotides having phosphorodithioate, phosphorothioamidate, phosphorothiotriesters and phosphorothioate internucleotide linkages.

The compound S-(2,4-dichlorobenzyl)-.beta.-cyanoethyl phosphorothioate diester is disclosed as useful in the synthesis of phosphorothioate oligonucleotides. In certain embodiments of the invention, this reagent is used to prepare 3'-S-(alkaryl) phosphorothioates. The .beta.-cyanoethyl blocking group can be removed and the resulting diester reacted with a nucleotide having a free 5'-hydroxyl group to yield compounds of the structure: ##STR1## where X is H, a first blocking group, a nucleoside, a nucleotide or an oligonucleotide; Y is H, a second blocking group, a nucleotide or an oligonucleotide; R is an alkaryl or aryl group; n is an integer greater than 0; and Bx is a heterocyclic base. Deblocking of the S-alkaryl or S-aryl moiety yields a phosphorothioate oligonucleotide.

Growing community of inventors

Kirkland, WA, United States of America

Eric K Yau