The present invention pertains to novel thiocycloheptyne derivatives of general formula (I): and in particular to thiacycloalkynesulfoimine derivatives and their synthesis. The invention also relates to the use of the novel thiocycloheptyne derivatives in coupling reactions with linkers and drugs. The invention further relates to the use of the novel thiocycloheptynes in bioorthogonal (copper-free) click reactions. The invention further pertains to the use of the novel thiocycloheptyne derivatives in the generation of advanced multifunctional drug delivery systems (drug-loaded) nanoparticles.

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This document relates to materials and methods for using controlled radical polymerization (e.g., atom transfer radical polymerization) to generate protein-polymer conjugates in which two or more polymer molecules are attached to individual initiator molecules on the protein.

This document relates to materials and methods for using controlled radical polymerization (e.g., atom transfer radical polymerization) to generate protein-polymer conjugates in which two or more polymer molecules are attached to individual initiator molecules on the protein.

The present disclosure provides therapeutic compositions and methods for delivering a therapeutic agent in close proximity to an analyte sensor. In certain embodiments, the present disclosure provides analyte sensors including one or more therapeutic agents, e.g., covalently-bound therapeutic agents. In certain embodiments, the present disclosure further provides therapeutic releasing compositions and methods of delivering such therapeutic releasing compositions.

The present disclosure provides therapeutic compositions and methods for delivering a therapeutic agent in close proximity to an analyte sensor. In certain embodiments, the present disclosure provides analyte sensors including one or more therapeutic agents, e.g., covalently-bound therapeutic agents. In certain embodiments, the present disclosure further provides therapeutic releasing compositions and methods of delivering such therapeutic releasing compositions.

Embodiments of the present application relate to polymers for liquid phase oligonucleotide synthesis. Methods for making an oligonucleotide by liquid phase oligonucleotide synthesis, comprising dissolving a polyvalent hub having a plurality of functional groups in a solvent and contacting the polyvalent hub with one or more nucleoside analogs to form a first bioconjugate are also provided.

Embodiments of the present application relate to polymers for liquid phase oligonucleotide synthesis. Methods for making an oligonucleotide by liquid phase oligonucleotide synthesis, comprising dissolving a polyvalent hub having a plurality of functional groups in a solvent and contacting the polyvalent hub with one or more nucleoside analogs to form a first bioconjugate are also provided.

This present invention relates to a polymer of γ-glutamyl transpeptidase catalyzing hydrolysis-induced charge reversal. The polymer comprises a γ-glutamyl transpeptidase-responsive element represented by Formula (I). When the polymer is used as drug carrier for anticancer drug, it can have a long circulation time in the blood, and can realize a charge reversal from negatively charged or the neutral to positively charged around the tumor blood vessel region, so that the positively charged polymer effectively penetrates deep into the tumor tissue, fast entering into the tumor cells, and greatly improves the therapeutic effect of the drug on the tumor. This overcomes the problems of slow diffusion of traditional polymer drug carriers in tumors and weak interaction with tumor cells, and has great significance in the field of anticancer treatment in the medical field. ##STR00001##

This present invention relates to a polymer of γ-glutamyl transpeptidase catalyzing hydrolysis-induced charge reversal. The polymer comprises a γ-glutamyl transpeptidase-responsive element represented by Formula (I). When the polymer is used as drug carrier for anticancer drug, it can have a long circulation time in the blood, and can realize a charge reversal from negatively charged or the neutral to positively charged around the tumor blood vessel region, so that the positively charged polymer effectively penetrates deep into the tumor tissue, fast entering into the tumor cells, and greatly improves the therapeutic effect of the drug on the tumor. This overcomes the problems of slow diffusion of traditional polymer drug carriers in tumors and weak interaction with tumor cells, and has great significance in the field of anticancer treatment in the medical field. ##STR00001##

Residence structures, systems, and related methods are generally provided. Certain embodiments comprise administering (e.g., orally) a residence structure to a subject (e.g., a patient) such that the residence structure is retained at a location internal to the subject for a particular amount of time (e.g., at least about 24 hours) before being released. The residence structure may be, in some cases, a gastric residence structure. In some embodiments, the structures and systems described herein comprise one or more materials configured for high levels of active substances (e.g., a therapeutic agent) loading, high active substance and/or structure stability in acidic environments, mechanical flexibility and strength in an internal orifice (e.g., gastric cavity), easy passage through the GI tract until delivery to at a desired internal orifice (e.g., gastric cavity), and/or rapid dissolution/degradation in a physiological environment (e.g., intestinal environment) and/or in response to a chemical stimulant (e.g., ingestion of a solution that induces rapid dissolution/degradation). In certain embodiments, the structure has a modular design, combining a material configured for controlled release of therapeutic, diagnostic, and/or enhancement agents with a structural material necessary for gastric residence but configured for controlled and/or tunable degradation/dissolution to determine the time at which retention shape integrity is lost and the structure passes out of the gastric cavity. For example, in certain embodiments, the residence structure comprises a first elastic component, a second component configured to release an active substance (e.g., a therapeutic agent), and, optionally, a linker. In some such embodiments, the linker may be configured to degrade such that the residence structure breaks apart and is released from the location internally of the subject after a predetermined amount of time.