Disclosed herein, inter alfa, are compounds, compositions, and methods of use thereof in the sequencing of a nucleic acid.

Phosphoramidate-based monomers are provided for use in the synthesis of expandable polymers for nanopore-based sensing. Such monomers comprising a reporter construct that contain a first reporter code, a symmetrical chemical brancher bearing a translocation control element, and a second reporter code, wherein the ends of the reporter construct are attached to phosphoramidate-nucleoside. Related methods and products are also provided.

Phosphoramidate-based monomers are provided for use in the synthesis of expandable polymers for nanopore-based sensing. Such monomers comprising a reporter construct that contain a first reporter code, a symmetrical chemical brancher bearing a translocation control element, and a second reporter code, wherein the ends of the reporter construct are attached to phosphoramidate-nucleoside. Related methods and products are also provided.

Provided herein are reagents and methods for incorporating modified nucleotides into DNA and detecting DNA synthesis. In particular, haloalkyl-modified nucleobases are provided for incorporation into nucleic acids for detection by bioluminescent binding agents.

Provided herein are reagents and methods for incorporating modified nucleotides into DNA and detecting DNA synthesis. In particular, haloalkyl-modified nucleobases are provided for incorporation into nucleic acids for detection by bioluminescent binding agents.

Nucleoside or nucleotide analog compounds having the structure shown below, a method for preparing them, and applications in nucleic acid sequencing are disclosed. The compounds have formula (I): ##STR00001## wherein L.sub.1, L.sub.2, and L.sub.3 are each independently a covalent bond or a covalently linked group; B is a base or a base derivative selected from purines, pyrimidines, or analogs thereof; R.sub.1 is —OH, a phosphate group, or a nucleotide; R.sub.2 as H or a cleavable group; R.sub.3 is a detectable group or a targeting group; R.sub.5 is an inhibitory group; R.sub.4 is H, —NH.sub.2, or —OR.sub.6, wherein R.sub.6 is H or a cleavable group; and C is a cleavable group or a cleavable bond.

The present invention provides a compound of Formula (I) and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are PRMT5 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat cancer, sickle cell, and hereditary persistence of foetal hemoglobin (HPFH) mutations.

##STR00001##

The present invention provides a compound of Formula (I) and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are PRMT5 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat cancer, sickle cell, and hereditary persistence of foetal hemoglobin (HPFH) mutations.

##STR00001##

Embodiments of the present application relate to N-acetylgalactosamine-conjugated nucleosides. In particular, the N-acetylgalactosamine is installed on the nucleobase of the nucleosides through a wide variety of linkers. Methods of making N-acetylgalactosamine-conjugated nucleosides are also disclosed herein. N-acetylgalactosamine is a well-defined liver-targeted moiety and N-acetylgalactosamine-conjugated nucleosides may be used in the preparation of targeted delivery of oligonucleotide-based therapeutics.

Embodiments of the present application relate to N-acetylgalactosamine-conjugated nucleosides. In particular, the N-acetylgalactosamine is installed on the nucleobase of the nucleosides through a wide variety of linkers. Methods of making N-acetylgalactosamine-conjugated nucleosides are also disclosed herein. N-acetylgalactosamine is a well-defined liver-targeted moiety and N-acetylgalactosamine-conjugated nucleosides may be used in the preparation of targeted delivery of oligonucleotide-based therapeutics.