Tesamorelin: structure and analysis

What is Tesamorelin?

Tesamorelin is a synthetic analog of the full 44-amino-acid growth hormone-releasing hormone, modified at the N-terminus with a trans-3-hexenoyl group. It is built on the complete sequence rather than the 1-29 fragment that sermorelin and CJC-1295 without DAC use.

At 44 residues it is the longest GHRH-derived compound in this catalogue and among the longest synthetic peptides in it.

The trans-3-hexenoyl group is an acyl modification — a small unsaturated chain attached to the N-terminal amine — and its function is to slow enzymatic degradation of the native sequence.

How is Tesamorelin produced?

Assembled by solid-phase peptide synthesis: the chain is built one residue at a time on an insoluble resin support, then cleaved from the resin, deprotected and purified — most commonly by reversed-phase high-performance liquid chromatography. The purified material is lyophilized to a dry solid.

The impurity profile that appears on a certificate is a record of where that process was imperfect: deletion sequences from an incomplete coupling, truncated chains, and species retaining a protecting group.

What are the molecular figures for Tesamorelin?

Calculated from the formula C221H366N72O67S, not measured. The average molecular weight counts the natural abundance of each element's isotopes; the monoisotopic mass is the mass of the single most abundant isotopic composition, which is the figure a mass spectrometer is usually compared against.

Two masses describe this molecule and they are not the same number. The monoisotopic mass assumes every carbon is carbon-12; the tallest peak in the isotope envelope sits 2 carbon-13 substitutions above it, because for a molecule with 221 carbons that is the most probable composition. A specification or a database quoting the higher figure is not necessarily wrong — it is quoting the other peak, and both are given here.

Adducts, salts, modifications and multiply charged species all move an observed m/z away from any figure calculated here, and a certificate reports what was measured for a batch rather than what was expected of it.

What is the sequence of Tesamorelin?

Tesamorelin is 44 residues long. Written in the one-letter amino-acid code, as the cited record states it:

The sequence is what an identity test resolves. The mass a spectrometer is compared against is the mass this chain implies, which is why a single missing or substituted residue changes the result by an amount that cannot be mistaken for instrument variation — the deletion is detectable rather than invisible.

Sequence information describes the molecule, not the material in a vial. What establishes a specific batch is the identity method and result on its certificate.

How does Tesamorelin compare with related compounds?

Related compounds are not interchangeable. Published figures differ between them, and in this catalogue three compounds share a GHRH backbone while several share the same structural class — which is exactly why identity is confirmed analytically rather than inferred from the label.

How is the identity of Tesamorelin confirmed?

Mass spectrometry confirms both the 44-residue chain and the N-terminal acyl modification. The hexenoyl group adds a distinct mass increment, so unmodified sequence is a clearly detectable impurity rather than an ambiguous one.

The mass also separates this compound unambiguously from the two 1-29-based GHRH compounds in the catalogue, which are fifteen residues shorter.

Which impurities can appear in Tesamorelin?

Forty-four coupling steps make this the most demanding synthesis in the catalogue outside the recombinant protein. Deletion sequences are the dominant impurity class and are numerous, so chromatographic resolution is the limiting factor on how informative a purity figure can be.

Incomplete acylation is the modification-specific impurity. Because the acyl group increases hydrophobicity, modified and unmodified species separate reasonably well on reversed phase, so mass and retention tend to agree.

As with the other GHRH-derived compounds, the identity result is what establishes which member of the family is present. Sermorelin, CJC-1295 without DAC and this compound are three different molecules.

What does a certificate of analysis for Tesamorelin report?

A certificate for a batch of this material names the batch, names the issuing laboratory, and states for each parameter both the method used and the specification the result was measured against. Identity and purity are the two core results; net peptide content states how much of the fill weight is actually peptide.

A certificate belongs to a batch, not to a product line. When a new batch is released it is tested again, and the certificate published against it is that batch's certificate — a previous batch's result is never carried forward.

Is Tesamorelin for human use?

No. This page describes structure and analysis. It makes no claim about what this compound does, and none should be inferred from it. Material is supplied for laboratory research use only: it is not a drug, food, dietary supplement, cosmetic or medical device, it is not for human or veterinary consumption, and no dosing, administration or reconstitution guidance is provided for any such use.

References

• Tesamorelin — PubChem, National Library of Medicine
• Somatoliberin (GHRH) — human — UniProt Knowledgebase
• Tesamorelin — ChEMBL, European Bioinformatics Institute