Modified nucleotides for nucleic acid labeling

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

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435 6, 536 231, 536 271, C07H 1900, C07H 2102, C12Q 168

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056841426

ABSTRACT:
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##

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