摘要:
New sub-monomer synthetic methods for the preparation of peptide nucleic acid oligomeric structures are disclosed that provide for the synthesis of both predefined sequence peptide nucleic acid oligomers as well as random sequence peptide nucleic acid oligomers. Further these methods also provide for the incorporation of peptide nucleic acid units or strings of such units with amino acids or strings of amino acids in chimeric peptide nucleic acid-amino acid compounds. Further disclosed are methods of making random libraries of peptide nucleic acids using the fully preformed monomers.
摘要:
Nucleotide compositions containing aminooxy moieties are provided. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least one of the nucleoside moieties of the oligonucleotide is modified to include an aminooxy moiety.
摘要:
Nucleotide compositions containing aminooxy moieties are provided. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least one of the nucleoside moieties of the oligonucleotide is modified to include an aminooxy moiety.
摘要:
Nucleosides and oligonucleosides functionalized to include carbamate functionality, and derivatives thereof. In certain embodiments, the compounds of the invention further include steroids, reporter molecules, reporter enzymes, lipophilic molecules, peptides or proteins attached to the nucleosides through the carbamate group.
摘要:
Compositions and methods are provided for the treatment and diagnosis of diseases amenable to modulation of the production of selected proteins. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least one of the 2'-deoxyfuranosyl moieties of the nucleoside unit is modified. Treatment of diseases caused by various viruses and other causative agents is provided.
摘要:
Methods for preparing oligonucleotide analogs which have improved nuclease resistance and improved cellular uptake are provided. In preferred embodiments, the methods involve radical coupling of 3'- and 5'-substituted or 5'- and 3'-subutituted nucleosidic synthons.
摘要:
Compositions and methods are provided for the modulation of expression of the human ras gene in both the normal and activated forms. Oligonucleotides are provided that have methylene(methylimino) linkages alternating with phosphorothioate or phosphodiester linkages. Further oligonucleotides are provide that have a first region having a methylene(methylimino) linkage alternating with a phosphorothioate or phosphodiester linkage and a second region having phosphorothioate linkages. Such oligonucleotides can be used for diagnostics as well as for research purposes including methods for diagnosis, detection and treatment of conditions arising from the activation of the H-ras gene.
摘要:
Synthetic processes are provided wherein substituted silylalkyl phosphoramidites serve as coupling reagents for preparing phosphate, phosphorothioate, and other phosphorous-containing covalent linkages. Also provided are synthetic intermediates useful in such processes. h processes.
摘要:
This invention presents novel purine-based compounds for inclusion into oligonucleotides. The compounds of the invention, when incorporated into oligonucleotides are especially useful as "antisense" agents--agents that are capable of specific hybridization with a nucleotide sequence of an RNA. Oligonucleotides are used for a variety of therapeutic and diagnostic purposes, such as treating diseases, regulating gene expression in experimental systems, assaying for RNA and for RNA products through the employment of antisense interactions with such RNA, diagnosing diseases, modulating the production of proteins, and cleaving RNA in site specific fashions. The compounds of the invention include novel heterocyclic bases, nucleosides, and nucleotides. When incorporated into oligonucleotides, the compounds of the invention can be useful for modulating the activity of RNA.
摘要:
Novel compounds that mimic and/or modulate the activity of wild-type nucleic acids are provided. The novel compounds have modified internucleoside linkages which preferably replace naturally-occurring phosphodiester-5'-methylene linkages with four atom linking groups. Preferred linkages have structures such as, for example, CH.sub.2 --R.sub.A --NR.sub.1 --CH.sub.2, CH.sub.2 --NR.sub.1 --R.sub.A --CH.sub.2, R.sub.A --NR.sub.1 --CH.sub.2 --CH.sub.2, CH.sub.2 --CH.sub.2 --NR.sub.1 --R.sub.A, CH.sub.2 --CH.sub.2 --R.sub.A --NR.sub.1, or NR.sub.1 --R.sub.A --CH.sub.2 --CH.sub.2 where R.sub.A is O or NR.sub.2. These linkages are prepared from appropriately functionalized nucleosides and oligonucleotides.