Nucleic acids internally-derivatized with a texaphyrin metal complex and uses thereof
First Claim
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1. A conjugate comprising a texaphyrin metal complex bound to an internal linkage of an oligonucleotide or oligonucleotide analog, the conjugate having hydrolytic cleavage activity for ribonucleic acid.
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Abstract
Texaphyrin metal complex-oligonucleotide and -oligonucleotide analog conjugates are provided where the texaphyrin is bound to an internal linkage of the oligonucleotide or oligonucleotide analog, the conjugates having catalytic activity for the hydrolysis of ribonucleic acid. Further, conjugates demonstrating catalytic turnover are described, the conjugates being especially effective under conditions where the concentration of RNA target exceeds that of available conjugate.
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25 Claims
- 1. A conjugate comprising a texaphyrin metal complex bound to an internal linkage of an oligonucleotide or oligonucleotide analog, the conjugate having hydrolytic cleavage activity for ribonucleic acid.
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2. A conjugate comprising a texaphyrin metal complex bound to an internal linkage of an oligonucleotide or oligonucleotide analog, the conjugate having hydrolytic cleavage activity for ribonucleic acid wherein the texaphyrin metal complex has the formula:
- ##STR3## wherein M is a divalent metal cation or a trivalent metal cation having catalytic activity for hydrolysis of ribonucleic acid;
R1 -R4, R7 and R8 are independently hydrogen, halide, hydroxyl, alkyl, alkenyl, alkynyl, aryl, haloalkyl, nitro, formyl, acyl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, saccharide, carboxy, carboxyalkyl, carboxyamide, carboxyamidealkyl, amino, aminoalkyl, an oligonucleotide, an oligonucleotide analog, a catalytic group, an antibody, a steroid, a hormone, a peptide having affinity for a biological receptor, a sapphyrin molecule, or a couple that is coupled to an oligonucleotide, an oligonucleotide analog, a catalytic group, an antibody, a steroid, a hormone, a peptide having affinity for a biological receptor, or a sapphyrin molecule; R6 and R9 are independently selected from the groups of R1 -R4, R7 and R8, with the proviso that the halide is other than iodide and the haloalkyl is other than iodoalkyl; R5 and R10 -R12 are independently hydrogen, alkyl, alkenyl, alkynyl, aryl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, carboxyalkyl, carboxyamide, carboxyamidealkyl, amino, aminoalkyl, or a couple that is coupled to a saccharide, an oligonucleotide, an oligonucleotide analog, a catalytic group, an antibody, a steroid, a hormone, a peptide having affinity for a biological receptor, or a sapphyrin molecule; at least one of R1 -R12 is an oligonucleotide, oligonucleotide analog, or a couple that is coupled to an oligonucleotide or an oligonucleotide analog; and Z is an integer value less than or equal to 5.
- ##STR3## wherein M is a divalent metal cation or a trivalent metal cation having catalytic activity for hydrolysis of ribonucleic acid;
Specification