Abstract: Provided herein are GLP-1 receptor antagonists peptides and pharmaceutical compositions for the treatment of hypoglycemia. Further provided herein are methods of treating atypical hypoglycemia in patients that have become hyperinsulinemic, including those who become hyperinsulinemic after bariatric surgery.

Abstract: Provided herein are GLP-1 receptor antagonists peptides and pharmaceutical compositions for the treatment of hypoglycemia. Further provided herein are methods of treating atypical hypoglycemia in patients that have become hyperinsulinemic, including those who become hyperinsulinemic after bariatric surgery.

Abstract: Compositions comprising novel peptides and dimers that exhibit antagonist activity against FGF23 binding to Klotho are disclosed. Such peptides can be used to treat hypoparathyroidism and osteoporosis.

Abstract: A novel derivative of parathyroid hormone is provided that has an extended time of action relative to known native parathyroid hormone agonist peptides, while minimizing excessive action shortly after administration. Compositions comprising the novel parathyroid hormone conjugates can be used to treat hypoparathyroidism and osteoporosis.

Abstract: Disclosed herein are modified C-terminal fragments of FGF21 optimized for binding to Klotho ? or antagonizing FGF21 activity. FGF21 peptides modified to comprise modifications to the C-terminal amino acid sequence are disclosed that have enhanced activity at the FGF21 receptor. Additionally, conjugates formed between the optimized FGF21 peptide fragments and insulin like peptides or nuclear hormone receptor ligands are provided.

Abstract: Disclosed herein are modified C-terminal fragments of FGF21 optimized for binding to Klotho ? or antagonizing FGF21 activity. FGF21 peptides modified to comprise modifications to the C-terminal amino acid sequence are disclosed that have enhanced activity at the FGF21 receptor. Additionally, conjugates formed between the optimized FGF21 peptide fragments and insulin like peptides or nuclear hormone receptor ligands are provided.

Abstract: Provided herein are peptides and variant peptides that exhibit enhanced activity at the GLP-1 receptor, as compared to native glucagon.

Abstract: Disclosed herein are insulin agonist peptides conjugated to a glucagon analog wherein the insulin/glucagon conjugate is targeted to liver tissues upon administration to a patient.

Abstract: Modified glucagon peptides are disclosed having improved solubility and/or stability while retaining glucagon agonist activity. The glucagon peptides have been modified by the substitution of pyridyl-alanine for a native amino acid at one or more of positions 6, 10 or 13 and/or substitution with an amino acid in the D-conformation at position 20 or 21 compared to native glucagon.

Abstract: Provided herein are glucagon agonist peptides conjugated with thyroid hormone receptor ligands that are capable of acting at the thyroid hormone receptor. Also provided herein are pharmaceutical compositions and kits of the conjugates of the invention. Further provided herein are methods of treating a disease, e.g., a metabolic disorder, such as diabetes, obesity, metabolic syndrome and chronic cardiovascular disease, comprising administering the conjugates of the invention.

Abstract: Provided herein are GLP-1 agonist peptides conjugated with thyroid hormone receptor ligands that are capable of acting at the thyroid hormone receptor. Also provided herein are pharmaceutical compositions and kits of the conjugates of the invention. Further provided herein are methods of treating a disease, e.g., a metabolic disorder, such as diabetes, obesity, metabolic syndrome and chronic cardiovascular disease, comprising administering the conjugates of the invention.

Abstract: Prodrug formulations of insulin and insulin analogs are provided wherein the insulin peptide has been modified by an amide bond linkage of a dipeptide prodrug element. The prodrugs disclosed herein have extended half-lives and are converted to the active form at physiological conditions through a non-enzymatic reaction driven by chemical instability.

Abstract: Modified glucagon peptides are disclosed having improved solubility and/or stability while retaining glucagon agonist activity. The glucagon peptides have been modified by the substitution of pyridyl-alanine for a native amino acid at one or more of positions 6, 10 or 13 and/or substitution with an amino acid in the D-conformation at position 20 or 21 compared to native glucagon.

Abstract: Disclosed herein are modified C-terminal fragments of FGF21 optimized for binding to Klotho ? or antagonizing FGF21 activity. FGF21 peptides modified to comprise modifications to the C-terminal amino acid sequence are disclosed that have enhanced activity at the FGF21 receptor. Additionally, conjugates formed between the optimized FGF21 peptide fragments and insulin like peptides or nuclear hormone receptor ligands are provided.

Abstract: Provided herein are peptides and variant peptides that exhibit enhanced activity at the GLP-1 receptor, as compared to native glucagon.

Abstract: Disclosed herein are insulin agonist peptides conjugated to incretins wherein the incretin-insulin conjugate has agonist activity at the insulin receptor and the corresponding incretin receptor, and stimulates weight loss in an individual administered the compound.

Abstract: Single chain insulin analogs are provided having high potency and specificity for the insulin receptor. As disclosed herein optimally sized linking moieties can be used to link human insulin A and B chains, or analogs or derivatives thereof, wherein the carboxy terminus of the B25 amino acid of the B chain is linked to the amino terminus of the A1 amino acid of the A chain via the intervening linking moiety. In on embodiment the linking moiety comprises a polyethylene glycol of 6-16 monomer units and in an alternative embodiment the linking moiety comprises a non-native amino acid sequence derived form the IGF-1 C-peptide and comprising at least 8 amino acids and no more than 12 amino acid in length. Also disclosed are prodrug and conjugate derivatives of the single chain insulin analogs.

Abstract: Provided herein are peptides and variant peptides that exhibit enhanced activity at the GLP-1 receptor, as compared to native glucagon.

Abstract: Herein is reported a fusion polypeptide comprising i) one, two, three or four incretin receptor ligand polypeptides, and ii) one human immunoglobulin Fc-region, wherein at least one of the incretin receptor ligand polypeptides comprises an amino acid that is covalently conjugated to a lipid, and wherein each of the one, two, three or four incretin receptor ligand polypeptides is covalently conjugated by a peptide bond to a terminus of the human immunoglobulin Fc-region, whereby to each terminus of the human immunoglobulin Fc-region only a single incretin receptor ligand polypeptide is conjugated.

Abstract: Disclosed herein are insulin agonist peptides conjugated to a glucagon analog wherein the insulin/glucagon conjugate is targeted to liver tissues upon administration to a patient.