摘要:
Prodrugs of cyclic anthracyclin toxins comprising a hypoxia-activated trigger and are disclosed. In addition, methods of treating cancer using the compounds of the invention are disclosed.
摘要:
Compounds having particular interest as labels and various novel uses in diagnostics and therapeutics are provided which have structure (1) wherein R1 is a binding partner, a linker or H; a and b are 0 or 1, provided that the total of a and b is 0 or 1; A is N or C; X is S, O, —C(O)—, NH or NCH2R6; Y is —C(O)—; Z is taken together with A to form an aryl or heteroaryl ring structure comprising 5 or 6 ring atoms wherein the heteroaryl ring comprises a single O ring heteroatom, a single N ring heteroatom, a single S ring heteroatom, a single O and a single N ring heteroatom separated by a carbon atom, a single S and a single N ring heteroatom separated by a carbon atom, 2 N ring heteroatoms separated by a carbon atom, or 3 N ring heteroatoms at least two of which are separated by a carbon atom, and wherein the aryl or heteroaryl ring carbon atoms are unsubstituted with other than H or at least 1 nonbridging ring carbon atom is substituted with R6 or ═O; R6 is independently H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, NO2, N(R3)2, C≡N or halo, or an R6 is taken together with an adjacent R6 to complete a ring containing 5 or 6 ring atoms; R3 is a protecting group or H; and tautomers, solvates and salts thereof; and provided that where a is 0, b is 1, and R1 is in which D2 is independently hydroxyl, blocked hydroxyl, mono, di or triphosphate, or an oligodeoxyribonucleotide otherwise containing only the bases A, G, T and C; and D3 is H or OH; then Z is not unsubstituted phenyl. Also provided are novel intermediates and methods for the preparation and use of the structure (1) compounds.
摘要:
Oligomers which have substituents on the 2′ position are resistant to oligonucleases and furthermore can be derivatized to deliver reagents or drugs, to carry label, or to provide other properties.
摘要:
The invention relates to novel modified oligonucleotides, the construction thereof, and their use in oligonucleotide-based therapies. More specifically, the invention is to novel oligonucleotides having modified internucleoside linkages which are resistant to nucleases, having enhanced ability to penetrate cells, and which are capable of binding target oligonucleotide sequences in vitro and in vivo. The modified oligonucleotides of the invention are particularly useful in oligonucleotide-based therapies utilizing the modified oligonucleotides to interrupt protein synthesis or transcription or to otherwise inactivate messenger RNA or double stranded DNA.
摘要:
Novel oligomers are disclosed which have enhanced ability with respect to forming duplexes or triplexes compared with oligomers containing only conventional bases. The oligomers contain 7-deaza-7-substituted purines or related analogs. The oligomers of the invention are capable of (i) forming triplexes with various target sequences such as virus or oncogene sequences by coupling into the major groove of a target DNA duplex at physiological pH or (ii) forming duplexes by binding to single-stranded DNA or to RNA encoded by target genes. The oligomers of the invention can be constructed to have any desired sequence, provided the sequence normally includes one or more bases that is replaced with the analogs of the invention. Compositions of the invention can be used for diagnostic purposes in order to detect viruses or disease conditions.
摘要:
Oligomers which have substituents on the 2' position are resistant to oligonucleases and furthermore can be derivatized to deliver reagents or drugs, to carry label, or to provide other properties.
摘要:
Pseudonucleosides and pseudonucleotides are useful in the synthesis of oligomers which contain these components as a means to derivatize the resulting oligonucleotide to useful substituents such as chelators, intercalators, or lipophilic compounds. In general, these pseudonucleotide components are of the formula: ##STR1## wherein each Y is independently O or S; each X is independently H, PO.sub.3.sup.-2, an activated nucleotide synthesis coupling moiety, a protecting group, a nucleoside, a nucleotide or a nucleotide sequence, or comprises a solid support;F is a functional group capable of linking an additional moiety or said group already reacted to effect the binding of said additional moiety;.quadrature. is an organic backbone which does not contain additional F or Y-X substituents and which is either achiral even when the Y-X substituents are different, or is a single enantiomer of a chiral compound;with the proviso that at least one X is a nucleoside, nucleotide, nucleotide sequence, an activated nucleotide synthesis coupling moiety, or comprises a solid support, or F represents said functional group already reacted with an additional group. Oligonucleotides having the pseudonucleoside at the 3' terminus are particularly stable in vivo.
摘要:
Oligonucleotide analogs wherein one or more phosphodiester linkages between adjacent nucleotides are replaced by an formacetal/ketal type linkage are resistant to nucleases and do not need to exhibit the diastereomerism characteristic of many other oligonucleotide analogs, and thus are capable of strong hybridization to target RNA or DNA. These oligonucleotide analogs are useful in therapies which modulate gene expression using "antisense" or other specifically binding oligomers.