Sermorelin

Sermorelin is the first 29 residues of growth hormone releasing hormone, ending in a C-terminal amide. That fragment is the shortest one still recognised at the GHRH receptor, which is why the analogue is 29 residues rather than the full 44.

The sequence is modelled in the PepXtide structural library, where its computed weight of 3357.93 g/mol agrees with the published figure. The molecular formula is not printed: the engine counts one or two hydrogens more than the published formula at the terminal caps, and a formula that does not match the reference is worse than none.

The parent hormone was isolated in 1982 from human pancreatic islet tumours and characterised independently by two groups in the same year, establishing the 44-residue releasing factor. Work published in 1984 then showed that the first 29 residues, carried as the C-terminal amide, retain the full intrinsic activity of the parent in vitro, which is the finding this compound exists to exploit. Unlike the analogues that followed it, sermorelin carries no engineered substitution: it is the native sequence, truncated and amidated.

Its molecular target is the GHRH receptor, a 423-residue class B G-protein-coupled receptor of the secretin family, related to the VIP, PACAP and calcitonin receptors, which couples to adenylyl cyclase and raises intracellular cyclic AMP. That receptor identity is what distinguishes this family from the secretagogues that act at the ghrelin receptor, a class A receptor with entirely different signalling.

The absence of engineering is also the compound's chief chemical liability, and it is well documented. Dipeptidyl peptidase IV cleaves the native releasing factor at the bond following the N-terminal tyrosine, removing the first two residues and yielding an inactive fragment; a second, trypsin-like cleavage has also been described. Work published in 1989 showed that acetylating the N-terminus, methylating the N-terminal tyrosine, or substituting a D-tyrosine at position one each completely blocked that cleavage, and every later analogue in this family is a variation on that finding. Reported half-lives for the unmodified 1-29 fragment are correspondingly short, on the order of minutes.

The classical assay for this class is primary pituitary cell culture from rat or pig, in which releasing-factor analogues are ranked against one another; receptor-level work uses cyclic AMP accumulation in transfected HEK293 cells expressing the human receptor. Supplier technical data report water solubility around 1 mg/mL and storage at -20C, with identity confirmed by mass spectrometry, HPLC and capillary zone electrophoresis.