Cross-linking oligonucleotides

A compound of the formula

• where R1 is H, or a 1-(β-D-ribofuranosyl) or 1-(β-D-2-D-ribofuranosyl) group which is optionally substituted on one or more of its hydroxyl function with a Z group wherein Z independently is methyl or a phosphate, thiophosphate alkylphosphate or alkanephosphonate group, or a reactive precursor of said phosphate, thiophosphate, alkylphosphate or alkanephosphonate group which precursor is suitable for internucleotide bond formation;
• R3 is (CH2)q—(Y)r—(CH2)m—A″ where A″ is a group selected from chloro, bromo, iodo, SO2R′″, S+R′″R″″ and a radical which activates the carbon to which it is attached for nucleophilic substitution, where each of R′″ and R″″ is independently C1-6 alkyl or aryl or R′″ and R″″ together form a C1-6 alkylene bridge, or A″ is an intercalator group, a metal ion chelator or a reporter group;
• Y is a functional linking group selected from a group consisting of —O—, —S—, —NR′—, —NH—CO—, trifuluroacetamido and phtalimido phthalimido groups where R′ is H or C1-6 alkyl, and at least one of the (CH2)m and (CH2)q groups is directly linked to said —O—, —S—, —NR′—, NH—CO—, trifluoroacetamido and phtalimido phthalimido groups and the other of said (CH2)m and CH2)q groups is linked to the heterocyclic base with a carbon to carbon bond;
• each of m and q is independently 0 to 8, inclusive;
• r is 0 or 1 provided that when A″ is a group selected from chloro, bromo, iodo, SO2R′″, S+R′″R″″ and a radical which activates the carbon to which it is attached for nucleophilic substitution, then m is not 0;
• each of R4 and R6 is independently H, OR, SR, NHOR, NH2, or NH(CH2)tNH2where R is H or C1-6alkyl and t is an integer from 0 to 12.

A compound of the formula

• where R1 is H, or a 1-(β-D-ribofuranosyl) or 1-(β-D-2-deoxyribofuranosyl) group which is optionally substituted on one or more of its hydroxyl functions with a Z group wherein Z independently is methyl or a phosphate, thiophosphate, alkylphosphate or alkanephosphonate group, or a reactive precursor of said phosphate, thiophosphate, alkylphosphate or alkanephosphonate group which precursor is suitable for internucleotide bond formation;
• R3 is (CH2)q—(Y)r—(CH2)m—A″ and A″ is a reporter group;
• Y is a functional linking group selected from a group consisting of —O—, —S—, —NR′—, —NH—CO—, trifluoroacetamido and phtalimido phthalimido groups where R′ is H or C1-6 alkyl, and at least one of the (CH2)m and (CH2)q groups is directly linked to said —O—, —S—, —NR′—, NH—CO—, trifluoroacetamido and phtalimido phthalimido groups and the other of said (CH2)m and (CH2)q groups is linked to the heterocyclic base with a carbon to carbon bond;
• each of m and q is independently 0 to 8, inclusive;
• r is 0 or 1, and
• each of R4 and R6 is independently H, OR, SR, NHOR, NH2, or NH(CH2)tNH2 where R is H or C1-6alkyl and t is an integer from 0 to 12.

An oligonucleotide having at least one nucleotide of the formula

• wherein R1 is a 1-(β-D-ribofuranosyl) or 1-(β-D-2-deoxyribofuranosyl) group which is optionally substituted on one or more of its hydroxyl functions with a Z group wherein Z independently is methyl or a phosphate, thiophosphate, alkylphosphate or alkanephosphonate group;
• R3 is (CH2)q—(Y)r—(CH2)m—A and A is a reporter group;
• Y is a functional linking group selected from a group consisting of —O—, —S—, —NR′—, —NH—CO—, trifluoroacetamido and phtalimido phthalimido groups where R′ is H or C1-6 alkyl, and at least one of the (CH2)m and (CH2)q groups is directly linked to said —O—, —S—, —NR′—, NH—CO—, trifluoroacetamido and phtalimido phthalimido groups and the other of said (CH2)m and CH2)q groups is linked to the heterocyclic base with a carbon to carbon bond;
• each of m and q is independently 0 to 8, inclusive;
• r is 0 or 1, and
• each of R4 and R6 is independently H, OR, SR, NHOR, NH2, NH(CH2)tNH2 where R is H or C1-6alkyl and t is an integer from 0 to 12.

A compound having the formula

• wherein R1 is H, or a 1-(β-D-ribofuranosyl) or 1-(β-D-2-deoxyribofuranosyl) group which is optionally substituted on one or more of its hydroxyl functions with a Z group wherein Z independently is methyl or a phosphate, thiophosphate, alkylphosphate or alkanephosphonate group which precursor is suitable for internucleotide bond formation;
• R3 is —W-X, wherein W is a chemical linker arm selected from the group consisting of C1-12 alkylene, C2-12 alkylene and C2-12 alkynylene, and X is selected from the group consisting of OH, SH, NH2 and chemically blocked derivatives thereof;
• each of R4 and R6 is independently H, OR, SR, NHOR, NH2, or NH(CH2)tNH2 where R is H or C1-6 alkyl and t is an integer from 0 to 12
• with the proviso that when W is —CH2CH2—, then X is other than NH2.

A labeled oligonucleotide comprising at least one nucleotide unit of the formula

• wherein R1 is a 1-(β-D-ribofuranosyl) or 1-(β-D-2-deoxyribofuranosyl) group which is optionally substituted on one or more of its hydroxyl functions with a Z group wherein Z independently is methyl or a phosphate, thiophosphate, alkylphosphate or alkanephosphonate group which precursor is suitable for internucleotide bond formation;
• R3 is —W-A, wherein W is a chemical linker selected from the group consisting of C1-12 alkylene, C2-12 alkenylene and C2-12 alkynylene, and A is a reporter group;
• and
• each of R4 and R6 is independently H, OR, SR, NHOR, NH2, or NH(CH2)tNH2 where R is H or C1-6alkyl and t is an integer from 0 to 12.

A compound having the formula

• wherein R1 is H, or a 1-(β-D-ribofuranosyl) or 1-(β-D-2-deoxyribofuranosyl) group which is optionally substituted on one or more of its hydroxyl functions with a Z group wherein Z independently is methyl or phosphate, thiophosphate, alkylphosphate or alkanephosphonate group which precursor is suitable for internucleotide bond formation;
• R3 is —W-A, wherein W is a chemical linker arm selected from the group consisting of C1-12 alkylene, C2-12 alkenylene and C2-12 alkynylene, and A is a reporter group;
• and
• each of R4 and R6 is independently H, OR, SR, NHOR, NH2, or NH(CH2)tNH2 where R is H or C1-6alkyl and t is an integer from 0 to 12.