Nucleoside hydrogen phosphonodithioate diesters and activated phosphonodithioate analogues
Granted: October 15, 1996
Patent Number:
5565555
Novel hydrogen-phosphonodithioate compositions are provided which are particularly useful for forming internucleotide and internucleoside linkages in oligonucleosides or oligonucleotides, The oligonucleotides and analogs thereof made by using the hydrogen-phosphonodithioate compositions may be therapeutically useful as antiviral and anticancer agents and may have other therapeutic or diagnostic uses, A method for making the hydrogen-phosphonodithioates is provided as well as a method for…
Oligonucleotides with inverted polarity
Granted: June 18, 1996
Patent Number:
5527899
Oligonucleotides having tandem sequences of inverted polarity, i.e., oligonucleotides comprising regions of the formula: ##STR1## wherein --C-- symbolizes any method of coupling the nucleotide sequence of opposite polarity, are useful for forming an extended triple helix with a double-helical nucleotide duplex. The inverted polarity also stabilizes the single-strand oligonucleotides to exonuclease degradation.
Method and cyclic carbonates for nucleotide analogues
Granted: May 7, 1996
Patent Number:
5514798
An improved method for the preparation of acyclic nucleotide analogues comprises first condensing a cyclic carbonate with a purine or pyrimidine base and then reacting the alkylated base with an activated phosphonate. Novel cyclic carbonates are employed to yield the desired phosphonylmethoxyalkyl nucleotide analogues.
Aromatic compounds
Granted: April 30, 1996
Patent Number:
5512596
A composition comprising a compound of the formula: ##STR1## wherein: X is H or OH;Y is a group capable of hydrogen bonding to amino, guanidino, or imidazole function, or a group comprising an acidic hydrogen atom, a protected acidic group, or an anion;E is N or CR.sub.1, wherein R.sub.1 is H, OH, CN, F, Cl, Br, or I;A.sub.4, A.sub.5, and A.sub.6 are each independently N, CH, CR.sub.40 or CZ wherein R.sub.40 is R.sub.43, OR.sub.43, SR.sub.43, S(O)R.sub.43, S(O).sub.2 R.sub.43, or…
Pyrimidine derivatives for labeled binding partners
Granted: March 26, 1996
Patent Number:
5502177
A compound having the structure: ##STR1## wherein R.sup.1 is an oligonucleotide;a is 1 and b is 0;A is C or CH;X is S, O, NH or NCH.sub.2 R.sup.6 ;Z is taken together with A to form an aryl ring structure comprising 6 ring atoms wherein the aryl ring carbon atoms are unsubstituted with other than H or at least 1 nonbridging ring carbon atom is substituted with R.sup.6 or .dbd.O;R.sup.6 is independently H, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl,…
Oligonucleotide analogs containing thioformacetal linkages
Granted: February 27, 1996
Patent Number:
5495009
Modified oligomers containing at least one internucleoside linkage of the formula Y.sup.1 CX.sub.2 y.sup.2 wherein at least one of Y.sup.1 and Y.sup.2 is sulfur and the other is oxygen and wherein each X is the same or different and is a stabilizing substituent are disclosed. These oligomers show superior binding properties and are thus useful for binding target substances in analytical uses. Also disclosed are improved methods for synthesis of oligomers containing linkages of the…
Oligonucleotide having enhanced binding affinity
Granted: January 23, 1996
Patent Number:
5486603
The present invention relates to an oligonucleotide or analog thereof conjugated to a molecule comprising a structure, which structure (a) is of substantially fixed conformation; (b) contains, is directly attached to, or is attached to a carbon atom that is directly attached to, an first amine; and (c) contains, is directly attached to, or is attached to an atom that is directly attached to a phosphate, a second amine, or a cationic sulfur. In a preferred embodiment, the structure…
Oligonucleotides containing 5-propynyl pyrimidines
Granted: January 16, 1996
Patent Number:
5484908
Oligonucleotides with enhanced hybridization binding possessing 5-propynyluracil and/or 5-propynylcytosine in place of uracil and cytosine, respectively. These oligonucleotides are useful in traditional hybridization assays for detection of a specific DNA sequence.
2'modified nucleoside and nucleotide compounds
Granted: November 14, 1995
Patent Number:
5466786
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.
Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages
Granted: July 18, 1995
Patent Number:
5434257
Oligonucleotide analogs having one or more substitute linkages of the formula 2'/3'--S--CH.sub.2 --CH.dbd.5' or 2'/3'--O--CH.sub.2 --CH.dbd.5' between adjacent nucleomonomers are disclosed. The substitute linkage replace the usual phosphodiester linkage found in unmodified nucleic acids. The oligonucleotide analogs are easy to synthesize, stable in vivo, resistant to endogenous nucleases and are able to hybridize to target nucleic acid sequences in a sequence specific manner.
Non-nucleoside linkers for convenient attachment of labels to oligonucleotides using standard synthetic methods
Granted: May 9, 1995
Patent Number:
5414077
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,…
Oligonucleotides with inverted polarity
Granted: March 21, 1995
Patent Number:
5399676
Oligonucleotides having tandem sequences of inverted polarity, i.e., oligonucleotides comprising regions of the formula: ##STR1## wherein --C-- symbolizes any method of coupling the nucleotide sequence of opposite polarity,are useful for forming an extended triple helix with a double-helical nucleotide duplex. The inverted polarity also stabilizes the single-strand oligonucleotides to exonuclease degradation.
Oligonucleotide analogs with novel linkages
Granted: November 23, 1993
Patent Number:
5264562
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.
Oligonucleotide analogs with novel linkages
Granted: November 23, 1993
Patent Number:
5264564
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.
Exonuclease-resistant oligonucleotides
Granted: October 26, 1993
Patent Number:
5256775
A method is provided for making 3' and/or 5' end-capped oligonucleotides so as to render the oligonucleotide resistant to degradation by exonucleases. The exonuclease degradation resistance is provided by incorporating two or more phosphoramidate and phosphorocmonothioate and/or phosphorodithioate linkages at the 5' and/or 3' ends of the oligonucleotide, wherein the number of phosphoramidate linkages is less than a number which would interfere with hybridization to a complementary…
Anthraquinone-derivatives oligonucleotides
Granted: May 25, 1993
Patent Number:
5214136
Oligonucleotide sequences modified by conjugation to at least one unsubstituted or substituted anthraquinone at other than the 5' terminus have favorable properties in enhancing hybridization to target DNA or RNA without loss of specificity and show enhanced stability to nucleases.
Hydrogen phosphonodithioate compositions
Granted: March 16, 1993
Patent Number:
5194599
Novel hydrogen-phosphonodithioate compositions are provided which are particularly useful for forming internucleotide and internucleoside linkages in oligonucleosides or oligonucleotides. The oligonucleotides and analogs thereof made by using the hydrogen-phosphonodithioate compositions may be therapeutically useful as antiviral and anticancer agents and may have other therapeutic or diagnostic uses. A method for making the hydrogen-phosphonodithioates is provided as well as a method for…
Large scale synthesis of oligonucleotides and their associated analogs
Granted: November 17, 1992
Patent Number:
5164491
The present invention describes methods for the production of oligonucleotides under conditions which exploit the desirable characteristics, such as the property of sustaining high degrees of substitution, of functionalized organic polymeric supports while avoiding the sluggish kinetics and low rates of conversion which normally plague syntheses involving such solid supports. By employing the methods and materials disclosed, functionalized support, substituted to a degree of about 250…
