Patent ID: 6300483
Filing Date: 2001-10-09
Classification: A61K,C12N

Abstract:
A composition that induces cleavage of an RNA substrate, the composition comprising:5'-Z.sub.1 -Z.sub.2 -Z.sub.3 -3'wherein Z.sub.1 and Z.sub.3 are oligomeric sequences which (1) are comprised of nucleotides, nucleotide analogues, or both, or (2) are oligonucleotide analogues, wherein the oligomeric sequences specifically interact with the RNA substrate by hybridization,wherein Z.sub.2 consists of5'-X.sup.12 X.sup.13 X.sup.14 X.sup.15.1 -3', or5'-X .sup.12 X.sup.12 X.sup.13 X.sup.14 X.sup.15.1 -3',wherein Z.sub.2 is comprised of nucleotides, nucleotide analogues, or both, wherein the nucleotides and nucleotide analogues each have the structure ##STR3##wherein each B is independently adenin-9-yl, cytosin-1-yl, guanin-9-yl, uracil-1-yl, uracil-5-yl, hypoxanthin-9-yl, thymin-1-yl, 5-methylcytosin-1-yl, 2,6-diaminopurin-9-yl, purin-9-yl, 7-deazaadenin-9-yl, 7-deazaguanin-9-yl, 5-propynylcytosin-1-yl, 5-propynyluracil-1-yl, isoguanin-9-yl, 2-aminopurin-9-yl, 6-methyluracil-1-yl, 4-thiouracil-1-yl, 2-pyrimidone-1-yl, quinazoline-2,4-dione-1-yl, xanthin-9-yl, N.sup.2 -dimethylguanin-9-yl or a functional equivalent thereof,wherein each V is independently an O, S, NH, or CH.sub.2 group,wherein each W is independently selected from the group consisting of --H, --OH, --COOH, --CONH.sub.2, --CONHR.sup.1, --CONR.sup.1 R.sup.2, --NH.sub.2, --NHR.sup.1, --NR.sup.1 R.sup.2, --NHCOR.sup.1, --SH, SR.sup.1, --F, --ONH.sub.2, --ONHR.sup.1, --ONR.sup.1 R.sup.2, --NHOH, --NHOR.sup.1, --NR.sup.2 OH, --NR.sup.2 OR.sup.1, substituted or unsubstituted C.sub.1 -C.sub.10 straight chain or branched alkyl, substituted or unsubstituted C.sub.2 -C.sub.10 straight chain or branched alkenyl, substituted or unsubstituted C.sub.2 -C.sub.10 straight chain or branched alkynyl, substituted or unsubstituted C.sub.1 -C.sub.10 straight chain or branched alkoxy, substituted or unsubstituted C.sub.2 -C.sub.10 straight chain or branched alkenyloxy, and substituted or unsubstituted C.sub.2 -C.sub.10 straight chain or branched alkynyloxy, wherein the substituents are independently halogen, cyano, amino, carboxy, ester, ether, carboxamide, hydroxy, or mercapto, wherein R.sup.1 and R.sup.2 are, independently, substituted or unsubstituted alkyl, alkenyl, or alkynyl groups, where the substituents are independently halogen, cyano, amino, carboxy, ester, ether, carboxamide, hydroxy, or mercapto,wherein D and E are residues which together form a phosphodiester or phosphorothioate diester bond between adjacent nucleosides or nucleoside analogues or together form an analogue of an internucleosidic bond,wherein in X.sup.15.1, B is hypoxanthin-9-yl,wherein in X.sup.12, B is independently guanin-9-yl, hypoxanthin-9-yl or 7-deazaguanin-9-yl;wherein in X.sup.13 and X.sup.14, B is independently adenin-9-yl, 2,6-diaminopurin-9-yl, purin-9-yl or 7-deazaadenin-9-yl;wherein in X .sup.12, B is independently adenin-9-yl, cytosin-1-yl, guanin-9-yl, uracil-1-yl, uracil-5-yl, hypoxanthin-9-yl, thymin-1-yl, 5-methylcytosin-1-yl, 2,6-diaminopurin-9-yl, purin-9-yl, 7-deazaadenin-9-yl, 7-deazaguanin-9-yl, 5-propynylcytosin-1-yl, 5-propynyluracil-1-yl, isoguanin-9-yl, 2-aminopurin-9-yl, 6-methyluracil-1-yl, 4-thiouracil-1-yl, 2-pyrimidone-1-yl, quinazoline-2,4-dione-1-yl, xanthin-9-yl, N.sup.2 -dimethylguanin-9-yl or a functional equivalent thereof.