Abstract: A photocleavable heterobifunctional linker can include a structure of Formula (A) wherein coumarin is any coumarin or coumarin derivative; R, R9, and R10 are each independently a chemical moiety; R1 is a hydrogen, protecting group, leaving group, substrate, or capture entity; R2 is a hydrogen, hydroxyl, halide, alkoxy, anhydride, amino, protecting group, leaving group, substrate, or capture entity; L1 is a sub-linker; and L2 is a sub-linker. A capture device can include the photocleavable bifunctional linker having a structure of Formula (A) as provide herein, wherein R1 is a substrate. A method of capturing a target substance can include: providing the capture device having the photocleavable bifunctional linker with the structure of Formula (A) and contacting a target substance to the capture moiety such that the target substance is captured. Irradiating the linker with light can cleave the linker, thereby releasing the target substance from the substrate.

Abstract: A peptide can have a sequence of one of SEQ ID NOs: 78-91. A conformationally-constrained kinked peptide includes: a conformationally-constraining portion and a kinked portion linked to the conformationally-constraining portion that conformationally constrains the kinked portion having a peptide sequence of one of SEQ NOs: 78-97. A cell-targeting compound can include a conformationally-constrained kinked peptide having a peptide sequence of one of SEQ ID NOs: 78-97. The peptide sequence can be one of SEQ ID NOs: 78-97, or 78-91, or 92-97. A cell-targeting compound can include a conformationally-constrained kinked peptide linked to a branched linker with one branch arm linked to a specific targeting moiety and one branch arm linked to a general targeting moiety. The specific targeting moiety can be an antibody. The general targeting moiety can be a lipid or cholesterol derivative.

Abstract: A compound can be a pro-fluorophore peroxynitrite sensor that generates a fluorophore when cleaved by peroxynitrite, having a structure of Formula A: wherein: moiety A is an ER-targeting fluorophore; Y is a linker; and moiety B is a phenol, substituted or unsubstituted, wherein the structure of Formula A is less fluorescent than the ER-targeting fluorophore moiety A.

Abstract: A compound can be a pro-fluorophore peroxynitrite sensor that generates a fluorophore when cleaved by peroxynitrite, having a structure of Formula A: wherein: moiety A is an ER-targeting fluorophore; Y is a linker; and moiety B is a phenol, substituted or unsubstituted, wherein the structure of Formula A is less fluorescent than the ER-targeting fluorophore moiety A.

Abstract: A compound can be a fluorescent taxane derivative having a structure of Formula 1, salt, stereoisomer, tautomer, polymorph, or solvate thereof. Formula 1 can be defined as: L, L-NH, or L-NH—C?O is a linker; and R is a substituent, where —OH, —O?, —NH2, and NH—CH3 are examples. Examples of linkers can include glycine, beta-alanine, gamma-aminobutyric acid (GABA). Pharmaceutical compositions can include the compound and a pharmaceutically acceptable carrier, and may be configured for intravenous injection. The fluorescent taxane derivative can be used to treat cancer and non-cancer diseases. The fluorescent taxane derivative can be used to monitor cellular efflux and determine whether a cell will efflux paclitaxel.

Abstract: A compound can be a fluorescent taxane derivative having a structure of Formula 1, salt, stereoisomer, tautomer, polymorph, or solvate thereof. Formula 1 can be defined as: L, L-NH, or L-NH—C?O is a linker; and R is a substituent, where —OH, —O?, —NH2, and NH—CH3 are examples. Examples of linkers can include glycine, beta-alanine, gamma-aminobutyric acid (GABA). Pharmaceutical compositions can include the compound and a pharmaceutically acceptable carrier, and may be configured for intravenous injection. The fluorescent taxane derivative can be used to treat cancer and non-cancer diseases. The fluorescent taxane derivative can be used to monitor cellular efflux and determine whether a cell will efflux paclitaxel.

Abstract: A peptide can have a sequence of one of SEQ ID NOs: 78-91. A conformationally-constrained kinked peptide includes: a conformationally-constraining portion and a kinked portion linked to the conformationally-constraining portion that conformationally constrains the kinked portion having a peptide sequence of one of SEQ NOs: 78-97. A cell-targeting compound can include a conformationally-constrained kinked peptide having a peptide sequence of one of SEQ ID NOs: 78-97. The peptide sequence can be one of SEQ ID NOs: 78-97, or 78-91, or 92-97. A cell-targeting compound can include a conformationally-constrained kinked peptide linked to a branched linker with one branch arm linked to a specific targeting moiety and one branch ann linked to a general targeting moiety. The specific targeting moiety can be an antibody. The general targeting moiety can be a lipid or cholesterol derivative.

Abstract: A conformationally-constrained kinked peptide includes: a conformationally-constraining portion and a kinked portion linked to the conformationally-constraining portion that conformationally constrains the kinked portion, the kinked portion comprising an endosomal-disrupting peptide. The peptide can include a peptide sequence of one of SEQ ID NOs: 1, 5-38, or 40-54 or 61-69. The conformationally-constrained kinked portion can be a majority portion or minority of the peptide.

Abstract: A method of delivering a cargo agent into cytosol of a cell can include: providing the delivery system of one of the embodiments described herein having the first and second delivery platforms; and administering the delivery system to a cell so as to cause targeting of two features on the cell so as to: cause endocytosis of the first and second delivery platforms of the delivery system into a common endosome, destabilize the endosome of the cell having the delivery system, release the cargo agent from the second linker; and release the cargo agent from the destabilized endosome into cytosol of the cell. A method of treating a disease can include: performing the method of method of delivering a cargo agent into cytosol of a cell in a subject having a disease, wherein the cargo agent is a therapeutic agent for the disease.

Abstract: A conformationally-constrained kinked peptide includes: a conformationally-constraining portion and a kinked portion linked to the conformationally-constraining portion that conformationally constrains the kinked portion, the kinked portion comprising an endosomal-disrupting peptide. The peptide can include a peptide sequence of one of SEQ ID NOs: 1, 5-38, or 40-69. The conformationally-constrained kinked portion can be a majority portion or minority of the peptide.

Abstract: A method of delivering a cargo agent into cytosol of a cell can include: providing the delivery system of one of the embodiments described herein having the first and second delivery platforms; and administering the delivery system to a cell so as to cause targeting of two features on the cell so as to: cause endocytosis of the first and second delivery platforms of the delivery system into a common endosome, destabilize the endosome of the cell having the delivery system, release the cargo agent from the second linker; and release the cargo agent from the destabilized endosome into cytosol of the cell. A method of treating a disease can include: performing the method of method of delivering a cargo agent into cytosol of a cell in a subject having a disease, wherein the cargo agent is a therapeutic agent for the disease.

Abstract: A delivery system for introducing a cargo molecule into cytosol of a living cell can include: a first membrane binding element linked to an endosomal compartment disrupting element through a first linker having one or more anionic moieties; and a second membrane binding element linked to an exogenous cargo molecule through a second linker having one or more anionic moieties, the second linker having a region that is selectively cleavable, wherein the first and second membrane binding elements both induce endocytosis into an early/recycling endosome and the endosomal compartment disrupting element destabilizes the early/recycling endosome such that the exogenous cargo molecule is released from the second membrane binding element and into the cytosol of the living cell.

Abstract: Synthetic cholesterylamine-linkers can include derivatives of cholesterol, cholesteryl, or sitosteryl coupled through the linker to an agent for delivery into cells. The cholesterylamines are thought to mimic cholesterol in the capacity and mechanism for enhanced entry into cells. The configuration of the cholesterylamine-linker that is thought to provide for enhanced entry into cells includes a cholesterylamine that is coupled to a linker from the amine, and which linker includes a negative charge at a spatial distance from the amine of the cholesterylamine.

Abstract: Synthetic cholesterylamine-linkers can include derivatives of cholesterol, cholesteryl, or sitosteryl coupled through the linker to an agent for delivery into cells. The cholesterylamines are thought to mimic cholesterol in the capacity and mechanism for enhanced entry into cells. The configuration of the cholesterylamine-linker that is thought to provide for enhanced entry into cells includes a cholesterylamine that is coupled to a linker from the amine, and which linker includes a negative charge at a spatial distance from the amine of the cholesterylamine.

Abstract: The present invention relates to new synthetic receptors. More particularly, the present invention relates to the use of the synthetic receptors for delivering a protein, peptide, drug, prodrug, lipid, nucleic acid, carbohydrate or small molecule into a target cell via receptor-mediated endocytosis. According to the invention, novel synthetic mimics of cell surface receptors have been designed and methods for use of the same are disclosed.

Abstract: The present invention relates to new synthetic receptors. More particularly, the present invention relates to the use of the synthetic receptors for delivering a protein, peptide, drug, prodrug, lipid, nucleic acid, carbohydrate or small molecule into a target cell via receptor-mediated endocytosis. According to the invention, novel synthetic mimics of cell surface receptors have been designed and methods for use of the same are disclosed.

Abstract: The present invention relates to new synthetic receptors. More particularly, the present invention relates to the use of the synthetic receptors for delivering a protein, peptide, drug, prodrug, lipid, nucleic acid, carbohydrate or small molecule into a target cell via receptor-mediated endocytosis. According to the invention, novel synthetic mimics of cell surface receptors have been designed and methods for use of the same are disclosed.

Abstract: The present invention relates to new synthetic receptors. More particularly, the present invention relates to the use of the synthetic receptors for delivering a protein, peptide, drug, prodrug, lipid, nucleic acid, carbohydrate or small molecule into a target cell via receptor-mediated endocytosis. According to the invention, novel synthetic mimics of cell surface receptors have been designed and methods for use of the same are disclosed.

Abstract: The present invention relates to new synthetic receptors. More particularly, the present invention relates to methods for synthesizing preferred membrane-binding elements, preferably cholesterylamine derivatives, including 3?-amino-5-cholestene (3?-cholesterylamine) and related 3?-halides through i-steroid and retro-i-steroid rearrangements. The invention further relates to use of the synthetic receptors for delivering a protein, peptide, drug, prodrug, lipid, nucleic acid, carbohydrate or small molecule into a target cell via receptor-mediated endocytosis. According to the invention, novel synthetic mimics of cell surface receptors have been designed and methods for use of the same are disclosed.

Abstract: A delivery system for introducing a cargo molecule into cytosol of a living cell can include: a first membrane binding element linked to an endosomal compartment disrupting element through a first linker having one or more anionic moieties; and a second membrane binding element linked to an exogenous cargo molecule through a second linker having one or more anionic moieties, the second linker having a region that is selectively cleavable, wherein the first and second membrane binding elements both induce endocytosis into an early/recycling endosome and the endosomal compartment disrupting element destabilizes the early/recycling endosome such that the exogenous cargo molecule is released from the second membrane binding element and into the cytosol of the living cell.