Abstract: In one aspect, the disclosure provides cross-linked materials that include multivalent lectins with at least two binding sites for glucose, wherein the lectins include at least one covalently linked affinity ligand which is capable of competing with glucose for binding with at least one of said binding sites; and conjugates that include two or more separate affinity ligands bound to a conjugate framework, wherein the two or more affinity ligands compete with glucose for binding with the lectins at said binding sites and wherein conjugates are cross-linked within the material as a result of non-covalent interactions between lectins and affinity ligands on different conjugates. These materials are designed to release amounts of conjugate in response to desired concentrations of glucose. Depending on the end application, in various embodiments, the conjugates may also include a drug and/or a detectable label.

Abstract: Conjugates which comprise a drug and a ligand which includes a first saccharide; wherein the conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic or pharmacodynamic property of the conjugate is sensitive to serum concentration of a second saccharide. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.

Abstract: The present disclosure provides crystalline insulin-conjugates. The present disclosure also provides formulations, methods of treatment, methods of administering, and methods of making that encompass these crystalline insulin-conjugates.

Abstract: The present disclosure provides crystalline insulin-conjugates. The present disclosure also provides formulations, methods of treatment, methods of administering, and methods of making that encompass these crystalline insulin-conjugates.

Abstract: Conjugates which comprise a drug and a ligand which includes a first saccharide; wherein the conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic or pharmacodynamic property of the conjugate is sensitive to serum concentration of a second saccharide. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.

Abstract: Conjugates which comprise a drug and a ligand which includes a first saccharide; wherein the conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic or pharmacodynamic property of the conjugate is sensitive to serum concentration of a second saccharide. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.

Abstract: The disclosure provides cross-linked materials that include multivalent cross-linking agents that bind an exogenous target molecule; and conjugates that include two or more separate affinity ligands bound to a conjugate framework, wherein the two or more affinity ligands compete with the exogenous target molecule for binding with the cross-linking agents and wherein conjugates are cross-linked within the material as a result of non-covalent interactions between cross-linking agents and affinity ligands on different conjugates. The conjugates also include a drug.

Abstract: The present disclosure provides inter alia conjugates of formula (I): wherein n, R1, R2, Rx, Z, X, Y and Z are as defined herein. A conjugate of formula (I) can also be converted to a conjugate of formulae (II) or (III) as described herein. Without limitation, the conjugates can be used to make controlled release materials and chemical sensors.

Abstract: The present disclosure provides recombinantly expressed insulin polypeptides that comprise an N-linked glycan motif. The N-linked glycan motif is not present in wild-type insulins and enables the recombinant expression of glycosylated insulin polypeptides (e.g., in yeast cells). Based on results obtained with synthetic glycosylated insulin conjugates we predict that when these recombinant glycosylated insulin polypeptides are administered to a mammal, at least one pharmacokinetic or pharmacodynamic property of the glycosylated insulin polypeptide will be sensitive to serum concentrations of glucose (or an exogenous saccharide such as alpha-methyl mannose). Exemplary insulin polypeptides, polynucleotides encoding these insulin polypeptides, glycosylated insulin polypeptides, pharmaceutical formulations and sustained release formulations are provided in addition to methods of use and preparation.

Abstract: Conjugates which comprise a drug and a ligand which includes a first saccharide; wherein the conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic or pharmacodynamic property of the conjugate is sensitive to serum concentration of a second saccharide. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.

Abstract: The present invention relates to methods for synthesizing compounds of formula I or pharmaceutically acceptable salts thereof: I wherein each of X, Alk1, Alk2, and W are as defined and described herein.

Abstract: The present disclosure provides crystalline insulin-conjugates. The present disclosure also provides formulations, methods of treatment, methods of administering, and methods of making that encompass these crystalline insulin-conjugates.

Abstract: The disclosure provides cross-linked materials that include multivalent cross-linking agents that bind an exogenous target molecule; and conjugates that include two or more separate affinity ligands bound to a conjugate framework, wherein the two or more affinity ligands compete with the exogenous target molecule for binding with the cross-linking agents and wherein conjugates are cross-linked within the material as a result of non-covalent interactions between cross-linking agents and affinity ligands on different conjugates. The conjugates also include a drug.

Abstract: Conjugates which comprise a drug and a ligand which includes a first saccharide; wherein the conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic or pharmacodynamic property of the conjugate is sensitive to serum concentration of a second saccharide. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.

Abstract: The present disclosure provides crystalline insulin-conjugates. The present disclosure also provides formulations, methods of treatment, methods of administering, and methods of making that encompass these crystalline insulin-conjugates.

Abstract: The disclosure provides cross-linked materials that include multivalent cross-linking agents that bind an exogenous target molecule; and conjugates that include two or more separate affinity ligands bound to a conjugate framework, wherein the two or more affinity ligands compete with the exogenous target molecule for binding with the cross-linking agents and wherein conjugates are cross-linked within the material as a result of non-covalent interactions between cross-linking agents and affinity ligands on different conjugates. The conjugates also include a drug.

Abstract: Methods for reducing the T-cell mitogenicity of lectin compositions are provided. In one aspect this is achieved by chemically modifying mitogenic lectin compositions under optimized conditions. Additionally or alternatively, the reduction in T-cell mitogenicity is achieved by removing unmodified subunits chemically modified mixtures. Modified lectin compositions with reduced T-cell mitogenicity are also provided as are uses of the inventive compositions.

Abstract: The present disclosure provides inter alia conjugates of formula (I): wherein n, R1, R2, Rx, Z, X, Y and Z are as defined herein. A conjugate of formula (I) can also be converted to a conjugate of formulae (II) or (III) as described herein. Without limitation, the conjugates can be used to make controlled release materials and chemical sensors.

Abstract: A conjugate that includes a drug covalently linked to a polymer. Upon administration, the conjugate is digested by an enzyme that is present at the site of administration thereby releasing a therapeutic agent. The conjugate may demonstrate substantially the same pharmacokinetic and pharmacodynamic behavior as the drug itself. A material for controllably releasing a conjugate in response to the local concentration of a molecular indicator. The material includes a plurality of conjugates and a plurality of multivalent cross-linking agents. The polymers of the conjugates include an analog of the indicator within their covalent structure. The multivalent cross-linking agents include cross-link receptors that interact with the indicator analog and thereby cross-link the conjugates.

Abstract: In one aspect, the disclosure provides a conjugate comprising an insulin molecule having an A-chain and a B-chain; an affinity ligand covalently bound to the A-chain; and a monovalent glucose binding agent covalently bound to the B-chain, wherein the affinity ligand competes with glucose for non-covalent binding with the monovalent glucose binding agent. In the absence of glucose, the monovalent glucose binding agent binds the affinity ligand to produce a “closed” inactive form of the insulin molecule. When free glucose is added, it competes with the affinity ligand for binding with the monovalent glucose binding agent to produce an “open” active form of the insulin molecule. The monovalent glucose binding agent and affinity ligand are covalently bound to the insulin molecule. The disclosure also provides methods of using these conjugates and methods of making these conjugates. In another aspect, the disclosure provides exemplary conjugates.