A bio-related substance bonded to a branched and degradable polyethylene glycol derivative that is degraded in the cells represented by the following formula (A):

##STR00001##

wherein each symbol is as defined in the present specification, is provided by the present invention.

Disclosed herein are calcitonin mimetics that are acylated at a lysine residue located at the 11 position or 19 position of the calcitonin mimetic, and the use thereof as medicaments in the treatment of various diseases and disorders, including diabetes, excess bodyweight, excessive food consumption and metabolic syndrome, NASH, alcoholic and non-alcoholic fatty liver disease, the regulation of blood glucose levels, the regulation of response to glucose tolerance tests, the regulation of food intake, and the treatment of osteoporosis and the treatment of osteoarthritis.

Disclosed herein are calcitonin mimetics that are acylated at a lysine residue located at the 11 position or 19 position of the calcitonin mimetic, and the use thereof as medicaments in the treatment of various diseases and disorders, including diabetes, excess bodyweight, excessive food consumption and metabolic syndrome, NASH, alcoholic and non-alcoholic fatty liver disease, the regulation of blood glucose levels, the regulation of response to glucose tolerance tests, the regulation of food intake, and the treatment of osteoporosis and the treatment of osteoarthritis.

A multi-arm, degradable polyethylene glycol derivative with a high molecular weight that does not cause vacuolation of cells is provided. A degradable polyethylene glycol derivative represented by the following formula (1):

##STR00001##

wherein n1 and n2 are each independently 45-950, W.sup.1 and W.sup.2 are each independently an oligopeptide of 2-47 residues, a1 and a2 are each independently 1-8, Q is a hydrocarbon chain having 2-12 carbon atoms and optionally containing an oxygen atom and/or a nitrogen atom, X.sup.1 and X.sup.2 are each independently a functional group capable of reacting with a bio-related substance, and L.sup.1, L.sup.2, L.sup.3, L.sup.4, L.sup.5 and L.sup.6 are each independently a divalent spacer.

The present invention generally relates to peptides with no or substantially reduced fibrillation and their therapeutic uses, in particular to phosphorylated calcitonin peptides that have no measureable or substantially reduced fibrillation in an aqueous environment. Also described herein are pharmaceutical compositions of such compounds and methods for treating a patient suffering from pain, osteoporosis, Paget's disease, and/or hypercalcemia by administering therapeutically effective amounts of such compound alone, or together with other therapeutics, or in a pharmaceutical composition to a patient in need of relief.

The present invention generally relates to peptides with no or substantially reduced fibrillation and their therapeutic uses, in particular to phosphorylated calcitonin peptides that have no measureable or substantially reduced fibrillation in an aqueous environment. Also described herein are pharmaceutical compositions of such compounds and methods for treating a patient suffering from pain, osteoporosis, Paget's disease, and/or hypercalcemia by administering therapeutically effective amounts of such compound alone, or together with other therapeutics, or in a pharmaceutical composition to a patient in need of relief.

The present invention relates generally to novel multi-agonist peptides useful as agents for the treatment and prevention of metabolic diseases and disorders, for example those which can be alleviated by control of weight loss, plasma glucose and lipid levels, insulin levels, and/or insulin secretion, positive inotropic effects, reduction of catabolic effects, slowing of gastric emptying and preventing neurodegeneration. Such conditions and disorders include, but are not limited to, control of food intake, weight loss, energy metabolism, plasma glucose levels, insulin levels, and/or insulin secretion, positive inotropic effects, reduction of catabolic effects, slowing of gastric emptying, obesity, diabetes and diabetes-related conditions, liver fat-associated inflammation and injury.

The present invention provides peptides and pharmaceutical compositions thereof for appetite suppression and weight control. Preferred peptides are calcitonin analogs preferably with specific amino acid changes to make the peptide more amylin-like.

The present invention provides peptides and pharmaceutical compositions thereof for appetite suppression and weight control. Preferred peptides are calcitonin analogs preferably with specific amino acid changes to make the peptide more amylin-like.

Analogs for CLR/RAMP receptor ligands are provided that have agonist, superagonist, antagonist, super-antagonist, or multiple receptor modulatng activity. The analogs can be selective for one or more CLR/RAMP receptors, or can be pan-specific for multiple G protein-coupled receptors.