Yale University

University of South Alabama

Oncor, Inc.

Codon Pharmaceuticals, Inc.

Canal House Biosciences, LLC

Jay George

Peter M Glazer

Yuxiang Gan

Nrusingha C Mishra

L Michael Lin

Pam Szweda

Hossein S Khorshidi

Robert W Sobol

The present invention relates to methods for the treatment of cancers, as well as pharmaceutical preparations of compounds useful in such treatments.

Cancer treatment

Methods, compositions and kits for effecting homologous recombination are described. In one aspect, the method utilizes two introduced DNAs: (1) a mutagen-linked single-stranded oligonucleotide capable of specifically binding to double-stranded DNA to form a triple-stranded helix, and (2) a donor DNA fragment capable of undergoing homologous recombination with DNA targeted by the oligonucleotide.

Methods and compositions for effecting homologous recombination

Modified pyrimidine bases and nucleotides containing a linker arm and a detectable reporter group for nucleic acid labeling. The modified nucleotides have the structure: ##STR1## wherein: -R.sub.1 is --H or --OH; -R.sub.2 and -R.sub.3 are independently --H, --OH, monophosphate, diphosphate, triphosphate, thio analogs of mono-, di-, or triphosphates, --O-- attached to a reactive phosphorous-containing group or --O-- protected by a blocking group; -A and -B are independently --H, an electron donating group, an electron withdrawing group, C.sub.1 -C.sub.4 alkyl, halogen, nitro, --COOH, amino, substituted amino, cyano, --CONH, --CSNH, --COOR.sub.4 ##STR2## --CSOR.sub.4, --COSR.sub.4, --SR.sub.4, --COR.sub.4, --CH.sub.2 NHR.sub.4, -R.sub.4 C.dbd.CR.sub.5 H or --C.tbd.C--R.sub.4 where R.sub.4 and R.sub.5 are independently H, an electron donating group, an electron withdrawing group, C.sub.1 -C.sub.4 alkyl, halogen, nitro, COOH, amino, substituted amino, cyano, CONH or CSNH; -X- is --NH--, --NHNH--, --O--, --S--, ##STR3## or --CH.sub.2 --; Rep is a detectable reporter group; and -L- is --(CH.sub.2).sub.n -(T).sub.q --(CH.sub.2).sub.m Z.sub.1 or --(CH.sub.2).sub.n -(T).sub.q --(CH.sub.2).sub.m -Z.sub.2 --(CH.sub.2).sub.p Z.sub.1 where n, m and p are each independently an integer from 1 to 20 and q is 1 or 2, -T- is --O--, --S--, ##STR4## --NH-- or a heterocyclic structure containing one or more Group Va or VIa elements as a ring atom, Z.sub.1 is a covalent bond, --NH--, --CO--, --O--, --S-- or ##STR5## and -Z.sub.2 -- is --NH--, --NHCO--, --NHCS--, --CONH--, --CSNH--, --O--, --S-- or ##STR6##

Modified nucleotides for nucleic acid labeling

Growing community of inventors

Gaithersburg, MD, United States of America

Jay George