What Is Tesamorelin? Structure and Chemistry

Tesamorelin is a synthetic analogue of GHRH: a single linear chain of forty-four amino acid residues with the sequence of GHRH(1–44), carrying an N-terminal trans-3-hexenoyl group. That acyl group is a six-carbon chain with one carbon–carbon double bond in the E (trans) configuration, attached to the amine of the N-terminal tyrosine. Its molecular formula is C221H366N72O67S, its average molecular weight is 5135.9 g/mol and its CAS number is 218949-48-5.

At more than 5 kDa, tesamorelin is one of the larger synthetic peptides in our catalogue, and its chemistry is dominated by two things: the length of the chain and the single modification at its start. This page covers both, then works through the formula and mass, the way a molecule of this size is analysed, the related substances to look for and what to check on a certificate.

Identity: a full-length chain with one added group

The description "a GHRH(1–44) analogue" packs in two facts. The bracketed numbers follow the standard fragment convention and name residues 1 to 44 of the parent sequence, which here is its full length, so tesamorelin carries the complete chain rather than a shortened fragment. "Analogue" records the one change: an acyl group bonded to the N-terminus.

In tesamorelin the chain is built from standard amino acids, and the structural interest sits in a single six-carbon group at one end. The GHRH, GHS-R & IGF-1 Analogues research area groups tesamorelin with the other peptides in this class.

The trans-3-hexenoyl group

The acyl group comes from trans-3-hexenoic acid, (E)-hex-3-enoic acid, C6H10O2. Written out, the acyl unit is CH3–CH2–CH=CH–CH2–C(=O)–, numbered from the carbonyl carbon as C1, so the double bond lies between C3 and C4. The E descriptor means the two carbon chains on either side of the double bond sit on opposite sides, the trans arrangement.

The group is attached by an amide bond to the α-amine of tyrosine 1. Forming that bond releases one water, so the net addition to the peptide is C6H8O.

The acyl cap also changes the charge at the N-terminus. A free α-amine is protonated and positively charged near neutral pH; once it carries the hexenoyl group it becomes a neutral amide. The double bond is isolated rather than conjugated with the carbonyl, which keeps the group's ultraviolet absorbance weak, so in practice the chain's tyrosine and peptide bonds dominate the UV signal.

Formula, molecular weight and elemental composition

The single sulfur atom in the formula belongs to the chain's one methionine. There is no cysteine, so there is no thiol and no disulfide bridge to confirm. Removing the acyl unit, C6H8O, from the full formula gives the des-acyl chain, C215H358N72O66S, a useful reference mass when looking for material in which the cap is missing.

The elemental composition is worth having on hand, because some net peptide content methods work from total nitrogen.

With nitrogen at 19.6% of the molecular mass, a nitrogen-based net peptide content figure has to use this exact value, not a generic average for peptides. The method is explained in peptide purity vs net peptide content.

What the formula says about the chain

A quick sense check on any long peptide is its average residue mass. Taking the des-acyl chain, 5039.7 g/mol, removing the 18.0 g/mol of water carried by the two free termini and dividing by forty-four residues gives about 114 Da per residue. That sits squarely in the range typical of peptides built from standard amino acids, which average roughly 110 to 120 Da per residue, and it is consistent with a chain carrying no other added groups.

The formula also fixes what a mass spectrum should and should not show. With one sulfur atom there is exactly one methionine to oxidise, so a series of +16 Da steps beyond the first would point to something other than methionine. With no cysteine, there is no disulfide bridge and no 2 Da shift to look for.

Mass spectrometry of a 5 kDa peptide

A molecule of this size behaves differently in the mass spectrometer from a short peptide. In electrospray ionisation it picks up many protons at once, so the spectrum shows a series of multiply charged ions, a charge-state envelope, rather than one dominant [M+H]+ peak. From the average mass, a 5+ ion would sit near m/z 1028.2, a 6+ ion near m/z 857.0 and a 7+ ion near m/z 734.7.

Software then deconvolutes that series to a single neutral mass. Because each charge state gives the same neutral mass, agreement across the envelope is itself a check on the assignment. The result is compared with 5135.9 g/mol.

Isotopes matter at this scale. With 221 carbon atoms, a molecule containing only carbon-12 is no longer the most common form, so the monoisotopic peak at 5132.7166 Da is small and the tallest isotopic peak sits a few mass units higher. High-resolution instruments can resolve the individual isotope peaks within one charge state; lower-resolution instruments report the envelope's centroid, which corresponds to the average mass. Mass spectrometry and peptide identity covers both approaches.

HPLC of a long synthetic chain

Reversed-phase HPLC gives the purity figure, as the main peak's share of total peak area at low ultraviolet wavelength. For a chain of forty-four residues the method usually uses a wide-pore stationary phase and a shallow gradient, because a large peptide interacts with the column over a bigger surface and its related substances can differ from it by a single residue.

The hexenoyl group adds a short hydrocarbon chain to the N-terminus, which makes the full molecule somewhat more hydrophobic than the des-acyl chain, so the two separate cleanly. The methionine sulfoxide, more polar than the parent, usually elutes slightly earlier. HPLC and peptide purity explains how the main-peak percentage is calculated.

Related substances to look for

Two of these share the parent's exact mass, so they are invisible to mass spectrometry alone: the cis isomer of the acyl group, and the positional isomer with the double bond between C2 and C3. This is why a full analysis uses HPLC and LC-MS together, with each method covering what the other cannot.

Counter-ions and the solid form

Each basic group in a peptide pairs with a counter-ion, such as acetate or trifluoroacetate, when the peptide is isolated from purification. In a long chain the counter-ions are spread over a much greater molecular mass, so their share of the powder's weight depends on the ratio of basic groups to residues rather than on chain length alone. The certificate's net peptide content figure accounts for counter-ions and residual water together. Assembly of chains of this length is covered in solid-phase peptide synthesis.

Certificates, specification and storage

Our Tesamorelin is supplied at ≥99% purity (HPLC) as a lyophilised powder in a sealed 10 mg vial. When reading a certificate for tesamorelin, check that the product is identified as the N-terminally trans-3-hexenoylated GHRH(1–44) chain, that the deconvoluted mass matches 5135.9 g/mol, that the HPLC method states its detection wavelength, that the salt form is stated, and that the report carries a reference and an analysis date. How to read a peptide certificate of analysis walks through each line.

Store the sealed vial at 2–8 °C for short-term storage, or at −20 °C and below for long-term storage. Protect it from light and avoid repeated freeze-thaw cycles; limiting contact with air also protects the methionine. Storing lyophilised peptides explains why cold, dark and dry storage matters for a freeze-dried solid.

Tesamorelin sits in the GHRH, GHS-R & IGF-1 Analogues research area with ipamorelin and IGF-1 LR3, an eighty-three-residue recombinant polypeptide that is analysed in much the same way. Terms used on this page, such as deconvolution, charge state and des-acyl, are defined in the glossary.