Gonadorelin
A synthetic linear decapeptide (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH₂) with a pyroglutamate N-terminus and C-terminal glycinamide, characterized in peptide-ligand GPCR pharmacology research.
Molecular Profile
- Type
- Synthetic peptide (linear decapeptide, 10 residues)
- Molecular formula
- C55H75N17O13
- Molecular weight
- ~1,182.3 Da
- CAS number
- 33515-09-2
- Amino acids
- 10
- Sequence
- pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH₂
- Modification
- Pyroglutamate (pGlu) at the N-terminus; C-terminal glycinamide amidation. Both modifications are critical for receptor recognition and confer relative resistance to aminopeptidase and carboxypeptidase cleavage; primary plasma degradation occurs at the Gly6 position.
Mechanism & Target Class
Gonadorelin is a synthetic linear decapeptide that engages a seven-transmembrane Gq/G11-coupled class A GPCR as a structural binding partner. The cognate receptor is unusual among GPCRs in lacking a cytoplasmic C-terminal tail, a structural feature that slows β-arrestin-mediated internalization and is studied as the basis for frequency-dependent receptor behavior. Upon ligand binding, the structurally characterized coupling proceeds through phospholipase C-β, which hydrolyzes PIP₂ into IP₃ and DAG; IP₃ mobilizes intracellular Ca²⁺ and DAG activates protein kinase C in cell-based assay models. A defining property characterized in the literature is pulse-dependent receptor pharmacology: intermittent exposure and continuous receptor occupancy produce distinct receptor states, with sustained occupancy driving GRK-mediated phosphorylation, β-arrestin recruitment, receptor internalization, and progressive surface-density downregulation. The pyroglutamate N-terminus and C-terminal glycinamide are essential for receptor recognition and confer relative resistance to exopeptidase cleavage; primary plasma degradation occurs at the Gly6 position, contributing to ultrashort circulatory clearance.
Storage & Handling
- Lyophilized
- -20°C (−80°C recommended for long-term); lyophilized powder stable approximately 24 months under proper conditions.
- Handling
- Hygroscopic; keep sealed and dry. Protect from light and moisture. Aliquot to minimize freeze-thaw exposure.
Primary Database
References (24)
Reviews
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