Abstract: Novel compounds and compositions including those compounds, as well as methods of using and making the compounds are herein described. The compounds are useful in therapeutic applications, including modulation of disease or disease symptoms in a subject (e.g., mammal, human, dog, cat, horse). The compounds are useful as modulators of the mu opioid receptor (MOR) through their binding affinity with that receptor.

Abstract: The present invention provides novel stabilized crosslinked compounds having secondary structure motifs, libraries of these novel compounds, and methods for the synthesis of these compounds libraries thereof. The synthesis of these novel stabilized compounds involves (1) synthesizing a peptide from a selected number of natural or non-natural amino acids, wherein said peptide comprises at least two moieties capable of undergoing reaction to promote carbon-carbon bond formation; and (2) contacting said peptide with a reagent to generate at least one crosslinker and to effect stabilization of a secondary structure motif. The present invention, in a preferred embodiment, provides stabilized p53 donor helical peptides. Additionally, the present invention provides methods for disrupting the p53/MDM2 binding interaction comprising (1) providing a crosslinked stabilized ?-helical structure; and (2) contacting said crosslinked stabilized ?-helical structure with MDM2.

Abstract: A method of generating a compound having at least one biological activity of a peptide. The method includes identifying a biologically active peptide, providing a first monomer which contains terminal reactive moieties and at least one functionalizable group, providing a second monomer which contains terminal reactive moieties and at least one functionalizable group, and reacting first and second monomer under stereo-and/or regiochemically controlled conditions to yield a compound in which the monomers are attached by way of terminal reactive moieties.

Abstract: Described are methods for identifying targets in RNA molecules based on differences in RNA secondary structure related to sequence variances between different allelic forms. Also described are methods for identifying or developing small molecules which can be used to modulate a target RNA by creation of protein-small-molecule-RNA complexes, as well as compositions which include such small molecules and methods of using those small molecules and compositions.

Abstract: The present invention relates to methods for the detection of polymorphisms by substituting a base-modified nucleotide for a natural nucleotide in a polynucleotide. The base-modified nucleotide renders the polynucleotide more susceptible to cleavage at the sites of its incorporation than site consisting of natural nucleotides. The fragments obtained are then analyzed to determine the presence or absence of a polymorphism.

Abstract: Uridine analogs and techniques for making and using uridine analogs are disclosed in this invention. These uridine analogs include nucleoside phosphates having a 5-aminouracil group. These nucleotides can be incorporated into a nucleic acid as an unnatural base, as a substitute for uridine or thymine. The nucleic acid can then be treated with an oxidizing agent and an alkaline solution, which causes cleavage of the nucleic acid at the position of the unnatural base. The nucleoside phosphate analogs can be used in many ways, including measuring chemical interactions between nucleic acids and other compounds, or sequencing nucleic acids. Additional compounds can also be derivitized onto the amino group, allowing other functionalities to be added to the nucleoside phosphate, or to the nucleic acid incorporating the nucleoside phosphate.

Abstract: Novel compounds and compositions including those compounds, as well as methods of using and making the compounds are herein described. The compounds are useful in therapeutic applications, including modulation of disease or disease symptoms in a subject (e.g., mammal, human, dog, cat, horse). The compounds are useful as modulators of the mu opioid receptor (MOR) through their binding affinity with that receptor.

Abstract: The present invention relates to methods for the detection of polymorphism in polynucleotides by using hybridization of fragments of segments of a polynucleotide suspected of containing a polymorphism with an oligonucleotide having a sequence complementary to a fragment identifying the polymorphism and subsequent detection of incorporated labels in the oligonucleotide-fragment duplex.

Abstract: Methods are described for identifying an RNA target for an allele-specific RNA inhibitor by identifying a sequence variance in an RNA encoded by a gene of interest, and determining whether the secondary structure of the RNA comprising the variance differs from that of an otherwise identical RNA not comprising the variance.

Abstract: Uridine analogs and techniques for making and using uridine analogs are disclosed in this invention. These uridine analogs include nucleoside phosphates having a 5-aminouracil group. These nucleotides can be incorporated into a nucleic acid as an unnatural base, as a substitute for uridine or thymine. The nucleic acid can then be treated with an oxidizing agent and an alkaline solution, which causes cleavage of the nucleic acid at the position of the unnatural base. The nucleoside phosphate analogs can be used in many ways, including measuring chemical interactions between nucleic acids and other compounds, or sequencing nucleic acids. Additional compounds can also be derivitized onto the amino group, allowing other functionalities to be added to the nucleoside phosphate, or to the nucleic acid incorporating the nucleoside phosphate.

Abstract: The present invention is directed to novel base-modified nucleotides and methods for their use in the preparation and cleavage of modified polynucleotides.

Abstract: The present invention relates to methods for the detection of polymorphism in polynucleotides by using hybridization of fragments of segments of a polynucleotide suspected of containing a polymorphism with an oligonucleotide having a sequence complementary to a fragment identifying the polymorphism and subsequent detection of incorporated labels in the oligonucleotide-fragment duplex.

Abstract: The present invention relates to a method of synthesizing a polynucleotide with incorporation of a modified nucleotide.

Abstract: The present invention relates to methods for the analysis of polynucleotides including detection of variance in nucleotide sequence without the need for full sequence determination, full sequence determination of a polynucleotide, genotyping of DNA and labeling a polynucleotide fragment during the process of cleaving it into fragments.

Abstract: The present invention relates to a method of synthesizing a polynucleotide with incorporation of a modified nucleotide.

Abstract: Described are methods for identifying targets in RNA molecules based on differences in RNA secondary structure related to sequence variances between different allelic forms. Also described are methods for identifying or developing small molecules which can be used to modulate a target RNA by creation of protein-small-molecule-RNA complexes, as well as compositions which include such small molecules and methods of using those small molecules and compositions.

Abstract: The present invention relates to methods for the detection of polymorphism in polynucleotides by using hybridization of fragments of segments of a polynucleotide suspected of containing a polymorphism with an oligonucleotide having a sequence complementary to a fragment identifying the polymorphism and subsequent detection of incorporated labels in the oligonucleotide-fragment duplex.

Abstract: The present invention relates to methods for the analysis of polynucleotides including detection of variance in nucleotide sequence without the need for full sequence determination, full sequence determination of a polynucleotide, genotyping of DNA and labeling a polynucleotide fragment during the process of cleaving it into fragments.

Abstract: The present invention relates to methods for the analysis of polynucleotides including detection of variance in nucleotide sequence without the need for full sequence determination, full sequence determination of a polynucleotide, genotyping of DNA and labeling a polynucleotide fragment during the process of cleaving it into fragments.

Abstract: The present invention pertains to novel inhibitors of DNA glycosylases. The invention is based at least in part on the observation that specific substituted pyrrolidines, and analogs thereof, are capable of specifically inhibiting DNA glycosylases, e.g., as transition state analogs, and consequently are useful for modulation of DNA repair. Such compounds can, for example, be used for treating subjects having a disorder associated with excessive cell proliferation, such as in the treatment of various cancers. Furthermore, these glycosylase inhibitors can be used as anti-bacterial, anti-viral and anti-fungal agents.