The present disclosure relates to bifunctional compounds, which find utility as modulators of enhancer of zeste homolog 2 (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

The present disclosure provides, inter alia, bivalent small molecules and methods for treating or ameliorating the effects of a disease, such as long QT syndrome, or cystic fibrosis, in a subject, using the bivalent small molecules disclosed herein. Also provided are methods of identifying and preparing small molecule binders that target proteins of interest.

The present invention provides the modular design and assembly of novel targeting bio-conjugates, exclusively assembled by means of biotin-biotin binding element conjugation, comprising mono-biotinylated cell binding component, a tetrameric biotin-binding element, and mono-biotinylated payload for therapeutic and diagnostic purposes. In addition, there is provided a method of delivering the payload, such as therapeutic oligonucleotides, via mono-biotinylated targeting devices, such as antibodies or ligands, into eukaryotic cells by means of receptor-mediated endocytosis. The targeting bio-conjugates are suitable for use in the areas of medicine, pharmacy and biomedical research.

The present invention relates to a brain delivery protein, comprising a target binding antibody which binds to a target in a mammalian brain; two carrier moieties, each of which being capable of monovalent interaction with a protein expressed on a blood brain barrier (BBB) endothelial cell, wherein each of said carrier moieties is linked to a C-terminal end of the target binding antibody. The present invention moreover relates to use of such brain delivery proteins in therapy or diagnosis or for research of e.g. neurodegenerative disorders, and other brain diseases.

The present disclosure relates to a method for labeling a biomolecule, a fluorescent dye, or a nanoparticle compound with a radioisotope, comprising: (a) providing a cyclooctyne compound represented by the following formula (I) comprising the biomolecule, the fluorescent dye, or the nanoparticle compound which is bound to a cyclooctyne moiety of the cyclooctyne compound; and (b) reacting the cyclooctyne compound of formula (I) with a quinone compound represented by the following formula (II) to give a biomolecule, a fluorescent dye, or a nanoparticle compound labeled with the radioisotope: ##STR00001## in formula (I), (Z is the biomolecule, the fluorescent dye, or the nanoparticle compound) ##STR00002## in formula (II), (b is 0 or an integer from 1 to 10; L is CH.sub.2, —COO—, or —CONH—; M is the radioisotope).

This disclosure related to modular and programmable peptide-oligonucleotide chimeras comprising of peptide and oligonucleotide segments interlinked by an organic core are presented and their assembly as morphologically-tunable soft materials, for example, nanostructure compositions comprising a plurality of compounds comprising a peptide segment and an oligonucleotide segment interlinked by an organic core moiety.

The present invention provides, among other things, methods and compositions of formulating nucleic acid-containing nanoparticles for efficient delivery of payload in vivo such that the method and compositions can be used to generate mRNA vaccines.

Glycotargeting therapeutics are useful in the treatment of transplant rejection, autoimmune disease, food allergy, and immune response against a therapeutic agent.

The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.

Disclosed herein are compositions and methods for labeling cells using click chemistry reagents. The compositions and methods disclosed herein provide a specific and efficient means of localizing desired agents to a variety of cell types in vivo and in vitro. The compositions and methods disclosed herein can be used to deliver a variety of desired agents to a cell or population of cells to direct cell fate and/or cell differentiation.