Covalently linked oligonucleotide minor groove binder conjugates

Claim 1

An oligonucleotide minor groove binder combination comprising an oligonucleotide having a plurality of nucleotide units, a 3′-end and a 5′-end, and a minor groove binder moiety attached to at least one of said nucleotides through a linking group which covalently binds the minor groove binder moiety to the oligonucleotide, wherein the minor groove binder moiety is a radical of a molecule having a molecular weight of approximately 150 to approximately 2000 Daltons that binds in a non-intercalating manner into the minor groove of double stranded DNA, RNA or hybrids thereof with an association constant greater than approximately 10 3 M −1 ; wherein the minor groove binding moiety including the linking group is represented by the formula: R 1 —(R 6 N—Y 2 —CO) n —R 2 wherein Y 2 is a ring system consisting of a 6-membered aromatic ring condensed with a 5-membered ring having one double bond, the condensed ring system having 0 to 3 heteroatoms selected from the group consisting of N, S and O, each of the R 6 N and CO groups is attached to a ring carbon which is in a different ring of the condensed ring system, and which is the second ring atom, respectively, from one common bridgehead ring atom, the CO and NR 6 groups thereby positioning 2 non-bridgehead ring atoms between themselves on one side and 3 non-bridgehead ring atoms on the other side of the condensed ring system, the two non-bridgehead ring atoms on the one side being optionally substituted with an R 7 group, the three non-bridgehead ring atoms on the other side of the condensed ring system being optionally substituted with an R 3 group; wherein one of R 1 or R 2 is a linking group forming a covalent attachment to said oligonucleotide and the other of R 1 or R 2 is selected from the group consisting of H, F, Cl, Br, I, NH 2 , NHR 4 , N(R 4 ) 2 , N(R 4 ) 3 + , OH, OR 4 , SH, SR 4 , COR 4 , CONHR 4 , CON(R 4 ) 2 , R 4 , H 2 N(CH 2 ) m CO, CONH 2 , CONHR 4 and H 2 N(CH 2 ) m COO (CH 2 ) m S(CH 2 ) m C 6 H 4 NNC 6 H 4 ; R 3 is selected from the group consisting of F, Cl, Br, I, NH 2 , NHR 4 , N(R 4 ) 2 , N(R 4 ) 3 + , OH, OR 4 , SH, SR 4 , COR 4 , CONHR 4 , CON(R 4 ) 2 and R 4 , or the R 3 groups may form a 3, 4, 5 or 6 membered ring condensed to the Y 2 ring and substituted by one, two or three R 4 ; R 4 is an alkyl or cycloalkyl group having 1 to 20 carbons, an alkenyl or cycloalkenyl group having 1 to 20 carbons and 1 to 3 double bonds, a carbocyclic aromatic group of no more than 25 carbons, a heterocyclic aromatic group of no more than 25 carbons, a carbocyclic or heterocyclic arylalkyl group of no more than 25 carbons, where R 4 may be optionally substituted with 1, 2 or 3 F, Cl, Br, I, NH 2 , NHR 5 , N(R 5 ) 2 , N(R 5 ) 3 + , OH, OR 5 , SH, SR 5 , COR 5 , CONHR 5 , CON(R 5 ) 2 or R 5 groups; R 5 is alkyl of 1 to 6 carbons, R 6 and R 7 jointly form a 4, 5, or 6 membered ring, optionally an —O—, —S—, —NH—, —NCH 3 —, or N -lower alkyl group being part of said ring; m is an integer between 1 and 10; and n is an integer between of from 2 and 5.