Growth hormone releasing factor, written variously as GRF or GHRH, is a hypothalamic peptide of forty four residues. Sermorelin, CAS 86168-78-7, is GRF(1-29) amide, the shortest amino terminal fragment described as retaining full activity at the GHRH receptor in published assays. Tesamorelin, CAS 218949-48-5, is catalogued as a GRF(1-44) analog and carries a trans-3-hexenoic acid group attached at the amino terminal tyrosine, a modification introduced specifically to address the degradation liability of the unmodified factor.
Recorded molecular data separate them clearly. Sermorelin is C149H246N44O42S with an average mass of 3357.93. Tesamorelin is C221H366N72O67S with an average mass of 5135.9. The difference of roughly 1778 daltons reflects the fifteen additional residues of the full length factor plus the hexenoyl group. Both contain a single sulfur atom, consistent with the methionine in the GRF sequence. Residue sequences for the two are not held in our molecular dataset, so each is described here by fragment identity and modification rather than position by position.
The stability difference is the entire point of the modification. Growth hormone releasing factor carries a tyrosine at position one and an alanine at position two, which is the canonical substrate pattern for dipeptidyl peptidase 4. That enzyme removes the first two residues, and the truncated product is described in the literature as losing activity at the receptor. Sermorelin, with a free amino terminus, presents that substrate directly. The trans-3-hexenoic acid group on tesamorelin occupies the amino terminus and is described as conferring resistance to that cleavage, giving the modified analog a longer measured persistence in plasma in published work.
Length changes the practical picture in the laboratory. A forty four residue chain is a substantially harder solid phase synthesis than a twenty nine residue chain, accumulating more deletion and truncation byproducts, so purity verification at 214 or 220 nanometres carries more weight for the longer molecule, as does mass spectrometric confirmation against the theoretical mass of 5135.9. Both are lyophilized powders held at minus 20 degrees Celsius protected from light and moisture, reconstituted with gentle swirling rather than shaking since long amphipathic helices foam readily, refrigerated at 2 to 8 degrees Celsius in solution, and aliquoted against repeated freeze thaw. The methionine in each is oxidation prone, so headspace air is minimised.
Both act at the same receptor, which is what makes the comparison useful. Because the GHRH receptor is common to the pair, a study that runs them side by side is effectively isolating the contribution of chain length and amino terminal protection rather than comparing two pharmacologies. Laboratories select sermorelin when a short, well characterised fragment is sufficient and when rapid clearance is acceptable or even desirable, and select tesamorelin when the question concerns the full length factor or when enzymatic degradation would confound the measurement.
What remains unsettled is how much of the difference measured in plasma stability assays translates into differences at the receptor itself, since binding studies on the two do not always separate them as cleanly as degradation studies do. Comparative figures also vary with the enzyme preparation and species used, so numbers from different groups are not readily pooled.