Described herein are compounds and compositions for the amelioration of arthritis or joint injuries by inducing mesenchymal stem cells into chondrocytes.

Described herein are compounds and compositions for the amelioration of arthritis or joint injuries by inducing mesenchymal stem cells into chondrocytes.

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure (I) wherein R.sub.1 and R.sub.2 are each independently for each occurrence optionally substituted C.sub.10-C.sub.30 alkyl, optionally substituted C.sub.10-C.sub.30 alkenyl, optionally substituted C.sub.10-C.sub.30 alkynyl, optionally substituted C.sub.10-C.sub.30 acyl, or -linker-ligand; R.sub.3 is H, optionally substituted C.sub.1-C.sub.10 alkyl, optionally substituted C.sub.2-C.sub.10 alkenyl, optionally substituted C.sub.2-C.sub.10 alkynyl, alkylheterocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ω-aminoalkyls, ω-(substituted)aminoalkyls, ω-phosphoalkyls, ω-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; E is O, S, N(Q), C(O), N(Q)C(O), C(O)N(Q), (Q)N(CO)O, O(CO)N(Q), S(O), NS(O)2N(Q), S(O)2, N(Q)S(O)2, SS, O═N, aryl, heteroaryl, cyclic or heterocycle; and, Q is H, alkyl, ω-aminoalkyl, ω-(substituted)aminoalkyl, ω-phosphoalkyl or ω-thiophosphoalkyl.

##STR00001##

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure (I) wherein R.sub.1 and R.sub.2 are each independently for each occurrence optionally substituted C.sub.10-C.sub.30 alkyl, optionally substituted C.sub.10-C.sub.30 alkenyl, optionally substituted C.sub.10-C.sub.30 alkynyl, optionally substituted C.sub.10-C.sub.30 acyl, or -linker-ligand; R.sub.3 is H, optionally substituted C.sub.1-C.sub.10 alkyl, optionally substituted C.sub.2-C.sub.10 alkenyl, optionally substituted C.sub.2-C.sub.10 alkynyl, alkylheterocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ω-aminoalkyls, ω-(substituted)aminoalkyls, ω-phosphoalkyls, ω-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; E is O, S, N(Q), C(O), N(Q)C(O), C(O)N(Q), (Q)N(CO)O, O(CO)N(Q), S(O), NS(O)2N(Q), S(O)2, N(Q)S(O)2, SS, O═N, aryl, heteroaryl, cyclic or heterocycle; and, Q is H, alkyl, ω-aminoalkyl, ω-(substituted)aminoalkyl, ω-phosphoalkyl or ω-thiophosphoalkyl.

##STR00001##

Described herein is dioxolane-containing compound of formula (I) wherein (i) Rf.sup.1 and Rf.sup.2 are independently linear or branched perfluoroalkyi groups having with 1-8 carbon atoms and optionally comprise at least one catenated heteroatom, or (ii) Rf.sup.1 and Rf.sup.2 are bonded together to form a ring structure having 4-6 carbon atoms and optionally comprise one or more catenated heteroatoms; Rf.sup.2 is a linear or branched perfluoroalkyi groups having with 1-3 carbon atoms; and R.sup.4 and R.sup.5 are independently selected from H, F, Cl, a linear or branched alkyl group having 1-3 carbon atoms, optionally wherein the alkyl group comprises at least one of: fluorine, chlorine, a hydroxyl group, or a catenated heteroatom; for use in cleaning compositions, as an electrolyte solvent, as a heat transfer fluid, or a vapor phase soldering fluid. There is also provided a method of making the dioxolane-containing compound, comprising: contacting a 1,2-diol compound with a fluorinated ethylenically unsaturated compound in the presence of a base. ##STR00001##

Described herein is dioxolane-containing compound of formula (I) wherein (i) Rf.sup.1 and Rf.sup.2 are independently linear or branched perfluoroalkyi groups having with 1-8 carbon atoms and optionally comprise at least one catenated heteroatom, or (ii) Rf.sup.1 and Rf.sup.2 are bonded together to form a ring structure having 4-6 carbon atoms and optionally comprise one or more catenated heteroatoms; Rf.sup.2 is a linear or branched perfluoroalkyi groups having with 1-3 carbon atoms; and R.sup.4 and R.sup.5 are independently selected from H, F, Cl, a linear or branched alkyl group having 1-3 carbon atoms, optionally wherein the alkyl group comprises at least one of: fluorine, chlorine, a hydroxyl group, or a catenated heteroatom; for use in cleaning compositions, as an electrolyte solvent, as a heat transfer fluid, or a vapor phase soldering fluid. There is also provided a method of making the dioxolane-containing compound, comprising: contacting a 1,2-diol compound with a fluorinated ethylenically unsaturated compound in the presence of a base. ##STR00001##

The present invention relates to a method of preparation of -galactosyl ceramides compounds of formula (I): ##STR00001##
comprising a step a) of glycosylation of a compound of formula (II): ##STR00002##
with a compound of formula (III): ##STR00003##

The present invention relates to a method of preparation of -galactosyl ceramides compounds of formula (I): ##STR00001##
comprising a step a) of glycosylation of a compound of formula (II): ##STR00002##
with a compound of formula (III): ##STR00003##

The present invention provides a nucleic acid-containing lipid nanoparticle comprising an analog of a fatty acid ester of glycerol, and a nucleic acid, wherein the analog is not hydrolyzable by a lipase.

This invention relates to an acid labile surfactant. In particular, the surfactants of the present invention include a dioxolane or dioxane functional group which enables the surfactant to hydrolyze in an acidic environment. Surfactants of this type can be utilized to enhance protein solubilization/enzyme digestion. Following hydrolysis to destroy the surfactant (which may chromatographic issues), there are generally two components formeda hydrophilic one, and a hydrophobic one. By altering the chemistry of the hydrolysable linker, the polarity of the hydrophobic residue can be altered, allowing it to be solubilized by significantly less organic solvent, and to minimize the potential loss of peptide material and to expand the chromatographic conditions that can be utilized.