Compound monograph
Cosyntropin (ACTH 1-24)
Cosyntropin is the synthetic 1-24 fragment of adrenocorticotropic hormone, the melanocortin ligand of the MC2R branch.
01
Identity & nomenclature
Cosyntropin is the synthetic 1-24 fragment of adrenocorticotropic hormone, the melanocortin ligand of the MC2R branch.
Cosyntropin is ACTH(1-24). It is not full-length ACTH(1-39), not ACTH(4-10), and not alpha-MSH. A shared N-terminal sequence does not erase chain-length or terminal-processing differences, and 'ACTH' in a paper's abstract does not establish which preparation was used — some melanocortin experiments use capped or norleucine-substituted analogs.
Declared aliases and development codes: Tetracosactide, ACTH(1-24), alpha 1-24 corticotropin.
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Molecular properties
| Molecular formula | C136H210N40O31S |
|---|---|
| Molecular mass | 2933.48 Da |
| CAS Registry Number | 16960-16-0 |
| PubChem CID | 16129617 |
| UNII | 72YY86EA29 |
| One-letter sequence | SYSMEHFRWGKPVGKKRRPVKVYP |
Twenty-four residues, all L, with a free N-terminus and a free C-terminal carboxyl. No acetylation, no amidation, no ring. Note the first thirteen residues are shared with alpha-MSH — the terminal processing is what differs.
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Structural characteristics
MC2R is the melanocortin receptor that responds to ACTH rather than to the shorter melanocortin pharmacophore, and its function depends on the accessory protein MRAP. Work fixing MRAP orientation establishes that the requirement is for MRAP acting on the EXTRACELLULAR face of the membrane, not merely for trafficking the receptor to the surface. Receptor-chimera experiments explicitly using ACTH(1-24) locate the regions responsible for ligand specificity and MRAP dependence. A structural study of an ACTH-bound MC2R-MRAP1 complex is cited as Class B: whether its experimental ligand is equivalent to unmodified cosyntropin is not established here.
Terminal features: Free Ser1 amino terminus, Free Pro24 carboxyl terminus.
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Molecular targets & mechanisms
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Analytical considerations
Confirmation needs the basic internal sequence and the Pro24 terminus, with explicit tests for Met4 versus a substituted analog and for the absence of an N-acetyl cap or C-terminal amide. An ACTH immunoassay may recognise several ACTH-containing fragments and does not establish 24-residue identity. Conversely, a negative result in an MC2R assay lacking functional MRAP is not evidence that the material is wrong.
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Verified bibliography
- Adrenocorticotropic Hormone (ACTH) Responses Require Actions of the Melanocortin-2 Receptor Accessory Protein on the Extracellular Surface of the Plasma Membrane.current
Malik S, Dolan TM, Maben ZJ, Hinkle PM
The Journal of biological chemistry · 2015-09-30 · Journal Article
- Use of chimeric melanocortin-2 and -4 receptors to identify regions responsible for ligand specificity and dependence on melanocortin 2 receptor accessory protein.current
Hinkle PM, Serasinghe MN, Jakabowski A, Sebag JA, Wilson KR, Haskell-Luevano C
European journal of pharmacology · 2011-01-03 · Journal Article
- Structural basis of signaling regulation of the human melanocortin-2 receptor by MRAP1.current
Luo P, Feng W, Ma S, Dai A, Wu K, Chen X, Yuan Q, Cai X, Yang D, Wang MW, Eric Xu H, Jiang Y
Cell research · 2023-01-02 · Journal Article
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Methodology & citation verification
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