Tesamorelin

Tesamorelin is a synthetic 44-residue analogue of growth hormone-releasing hormone, distinguished from the native hormone by a single N-terminal acylation. It is one of three GHRH-family analogues in this library, and comparing the three is the clearest way to see how the same design problem — protecting the N-terminus from dipeptidyl peptidase-4 — has been solved in different ways.

Identity and classification

Tesamorelin is human GRF(1–44) amide bearing a trans-3-hexenoyl group on the N-terminal tyrosine. Its systematic description — trans-3-hexenoyl-hGRF(1–44)-NH₂ — states the whole modification.

A formula discrepancy worth knowing about

Sources disagree on the molecular formula. The FDA-approved prescribing information gives C₂₂₁H₃₆₆N₇₂O₆₇S. Wikipedia and at least one chemical database give C₂₂₀H₃₆₄N₇₂O₆₇S — one carbon and two hydrogens fewer.

We publish the FDA label figure. A regulatory filing for a marketed drug substance is a stronger source than a secondary database, and the mass of 5135.9 g/mol is consistent across the label and three commercial suppliers. If a certificate quotes the other formula, that is worth raising with the supplier — it may simply be copied from the wrong source, but it may indicate they have not characterised the material themselves.

Structure

The 44-residue sequence is the full-length human GHRH: YADAIFTNSYRKVLGQLSARKLLQDIMSRQQGESNQERGARARL, terminating in a C-terminal amide.

The trans-3-hexenoyl group — a six-carbon unsaturated acyl chain — is attached to the α-amino group of Tyr1. That single modification is the entire structural difference from native GRF(1–44), and its purpose is to block the dipeptidyl peptidase-4 cleavage site at the N-terminus. CJC-1295 addresses the same vulnerability by substituting D-alanine at position 2 instead; sermorelin does not address it at all.

Note the single methionine at position 27 — the sulfur in the molecular formula — and the absence of cysteine. There is no disulfide bond.

Salt form — this one matters

The marketed material is tesamorelin acetate, not the free peptide, with approximately seven acetate counter-ions per peptide molecule. The FDA label states the drug substance as C₂₂₁H₃₆₆N₇₂O₆₇S · x C₂H₄O₂ where x is around 7.

The practical consequence is a mass overhead of roughly 10%: 2 mg of tesamorelin corresponds to about 2.2 mg of tesamorelin acetate. A vial weighed out as acetate contains proportionally less peptide, and a specification that does not state which basis it uses is ambiguous about roughly a tenth of the contents.

The acetate has its own registry number, 901758-09-6, distinct from the free-peptide number. Many vendors list acetate material under the free-peptide CAS. Both numbers appear in the table above so the distinction is explicit.

Specification and characterisation

• RP-HPLC purity at 214 nm, with 280 nm informative via the three tyrosines and the phenylalanine.
• Mass confirmation against 5135.9 average. At 44 residues, ESI-MS produces a multiply-charged envelope requiring deconvolution.
• Methionine oxidation. Met27 gives a +16 Da sulfoxide, the principal chemical degradation product, visible as an earlier-eluting shoulder on reverse phase.
• Deletion sequences. A 44-residue synthesis is long. Single-residue deletions are the dominant synthesis-related impurity class and are the reason a purity figure on a peptide this size should be read alongside the method that produced it.
• Acylation completeness. The des-hexenoyl peptide — unmodified GRF(1–44) amide — is the characteristic impurity, and it is a different compound rather than merely a degraded one.
• Net peptide content and acetate determination. Given the roughly 10% counter-ion burden, this is not a formality for tesamorelin.

Handling and stability

Store sealed at 2–8 °C, dry, protected from light. Equilibrate in a desiccator before opening. Minimise oxygen exposure and repeated temperature cycling because of Met27.

Long peptides are more prone than short ones to aggregation and to adsorptive loss on labware at low concentration — a real source of quantitative error that is easy to attribute to the material instead of the handling.

Related compounds in this library

Sermorelin — GRF(1–29) amide, the truncated fragment with no protective modification. CJC-1295 — a tetrasubstituted GRF(1–29) analogue. The three together make a useful comparison set: same receptor family, three different structural strategies.

References

Chemical, specification and analytical sources. This list is deliberately limited to chemistry and analytical references.

• FDA prescribing information, EGRIFTA SV (022505s018) — molecular formula, molecular weight, acetate stoichiometry
• DailyMed, EGRIFTA SV label — drug substance description
• Pharmaffiliates, CAS 218949-48-5 — registry and mass data
• Abbiotec, tesamorelin acetate — salt form and registry
• Bachem, Handling and Storage Guidelines for Peptides — methionine oxidation, long-peptide handling

Cosmic Aminos supplies this material as a laboratory reagent for in-vitro research use only. It is not a drug, food, cosmetic or dietary supplement, is not approved by the Food and Drug Administration for any use, and is not for human or veterinary consumption. No dosing, administration or preparation guidance is provided.