A conjugate containing a fluorescent chromophore, which has any structure selected from C1 to C3. The conjugate containing the fluorescent chromophore provided by the described embodiments includes one fluorescent chromophore and two highly reactive groups R1 and R2 linked to the fluorescent chromophore by a covalent bond. The fluorescent chromophore in the conjugate initially has no or only weak fluorescence emission capability, and only after the two highly reactive groups react together with the corresponding molecule, the fluorescent chromophore has strong fluorescence emission. Therefore, the efficiency of conjugation of drug molecules to targeting molecules can be monitored in situ by the infrared fluorescence emission intensity and applied to the target-mediated drug delivery.

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A conjugate containing a fluorescent chromophore, which has any structure selected from C1 to C3. The conjugate containing the fluorescent chromophore provided by the described embodiments includes one fluorescent chromophore and two highly reactive groups R1 and R2 linked to the fluorescent chromophore by a covalent bond. The fluorescent chromophore in the conjugate initially has no or only weak fluorescence emission capability, and only after the two highly reactive groups react together with the corresponding molecule, the fluorescent chromophore has strong fluorescence emission. Therefore, the efficiency of conjugation of drug molecules to targeting molecules can be monitored in situ by the infrared fluorescence emission intensity and applied to the target-mediated drug delivery.

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Variant peptides of calcitonin gene-related peptide alpha (CGRP), calcitonin gene-related peptide beta (CGRP), and adrenomedullin (AM) are disclosed, wherein the variant peptides have high binding affinity and agonistic or antagonistic activity for at least one receptor complex of CLR:RAMP1, CLR:RAMP2, and CLR:RAMP3. Also disclosed are methods of use of the variant peptides in therapeutic treatments.

Variant peptides of calcitonin gene-related peptide alpha (CGRP), calcitonin gene-related peptide beta (CGRP), and adrenomedullin (AM) are disclosed, wherein the variant peptides have high binding affinity and agonistic or antagonistic activity for at least one receptor complex of CLR:RAMP1, CLR:RAMP2, and CLR:RAMP3. Also disclosed are methods of use of the variant peptides in therapeutic treatments.

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 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.

Variant peptides of calcitonin gene-related peptide alpha (CGRP), calcitonin gene-related peptide beta (CGRP), and adrenomedullin (AM) are disclosed, wherein the variant peptides have high binding affinity and agonistic or antagonistic activity for at least one receptor complex of CLR:RAMP1, CLR:RAMP2, and CLR:RAMP3. Also disclosed are methods of use of the variant peptides in therapeutic treatments.

Variant peptides of calcitonin gene-related peptide alpha (CGRP), calcitonin gene-related peptide beta (CGRP), and adrenomedullin (AM) are disclosed, wherein the variant peptides have high binding affinity and agonistic or antagonistic activity for at least one receptor complex of CLR:RAMP1, CLR:RAMP2, and CLR:RAMP3. Also disclosed are methods of use of the variant peptides in therapeutic treatments.

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.

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.