What Is Ipamorelin? Structure and Chemistry

Ipamorelin is a synthetic pentapeptide with the sequence H-Aib-His-D-2-Nal-D-Phe-Lys-NH2 and, by receptor class, a ghrelin receptor (GHS-R1a) ligand. Its molecular formula is C38H49N9O5, its average molecular weight is 711.85 g/mol and its CAS number is 170851-70-4. Three of its five residues are non-standard: α-aminoisobutyric acid (Aib), 3-(2-naphthyl)-D-alanine (D-2-Nal) and D-phenylalanine, and the chain ends in a C-terminal amide.

That makes ipamorelin one of the most modified short peptides in our catalogue. This page works through the molecule residue by residue, then covers its formula, mass and charge, how it is analysed, and what to look for on a certificate.

The ipamorelin sequence, residue by residue

Written in full, with both termini shown, the peptide is H-Aib-His-D-2-Nal-D-Phe-Lys-NH2. The "H-" is the free amine at the N-terminus and the "-NH2" is the C-terminal amide. PubChem gives the systematic name 2-methylalanyl-L-histidyl-3-(2-naphthyl)-D-alanyl-D-phenylalanyl-L-lysinamide, which names the same five residues in order. PubChem's own record writes the sequence as H-Aib-His-D-2Nal-D-Phe-Lys-NH2; "2-Nal" and "2Nal" are the same residue. The conventions behind this notation are covered in peptide sequence notation.

The pattern is compact: an achiral residue at the N-terminus, a basic heteroaromatic residue, two D-configured aromatic residues side by side, and a basic residue at the amidated C-terminus.

Three non-standard residues

Aib at position 1

α-Aminoisobutyric acid, also called 2-methylalanine, is alanine with a second methyl group in place of the α-hydrogen. PubChem lists the free amino acid as 2-amino-2-methylpropanoic acid, C4H9NO2, 103.12 g/mol. With two identical methyl groups on the α-carbon it has no stereocentre, so it has no D or L form, which is why it is written without a prefix.

An α,α-disubstituted residue like Aib has no α-hydrogen and a restricted range of backbone torsion angles. In solid-phase synthesis it is a sterically hindered building block that couples more slowly than most amino acids, a point covered in solid-phase peptide synthesis.

D-2-Nal at position 3

D-2-Nal is 3-(2-naphthyl)-D-alanine: alanine carrying a naphthalene ring on its β-carbon, attached through ring position 2. PubChem lists the free amino acid as (2R)-2-amino-3-naphthalen-2-ylpropanoic acid, C13H13NO2, 215.25 g/mol. It is non-proteinogenic, so it enters the chain as a protected synthetic building block. Its naphthalene side chain, two fused benzene rings, is the largest side chain in the molecule and accounts for ten of its 38 carbon atoms.

The "2" in the name matters. 1-Nal, with the ring attached through position 1, is a positional isomer with the same formula and mass, so the two can only be distinguished chromatographically or by a structural method.

D-Phe at position 4

D-Phenylalanine is the mirror-image form of the usual residue at its α-carbon. PubChem's IUPAC name for ipamorelin labels the D-2-Nal and D-Phe α-carbons (2R) and the histidine and lysine α-carbons (2S). In three-letter notation a D-residue always carries its prefix, while a residue written without one is L by convention, following the IUPAC-IUB recommendations for peptide symbols.

The C-terminal amide

In most peptides the last residue ends in a carboxylic acid, –COOH. In ipamorelin that group is an amide, –CONH2, written "-NH2" at the end of the sequence. The amide carries no charge and is 0.984 Da lighter than the free acid it replaces, which matters when the expected mass is checked.

Formula, molecular weight and charge

The formula can be checked by simple addition. The five residue formulas sum to C38H46N8O5. The free N-terminal hydrogen and the C-terminal NH2 together add NH3, giving C38H49N9O5, the formula PubChem lists.

The average molecular weight, 711.85 g/mol, is the catalogue value; PubChem rounds the same figure to 711.9 g/mol, and the current IUPAC abridged atomic weights give 711.87 g/mol. The differences reflect the atomic-weight table, not the molecule.

Ipamorelin has three basic groups: the free N-terminal amine on Aib, the side-chain amine of lysine and the imidazole ring of histidine. It has no acidic group, because the C-terminus is an amide. Near pH 7 the two amines are protonated while the imidazole, with a pKa near 6, is mostly neutral, so the net charge is about +2. At the acidic pH used in reversed-phase HPLC, all three groups are protonated.

That basic character also shapes the supplied solid. A basic peptide is isolated as a salt, with counter-ions such as acetate or trifluoroacetate paired with its positive groups, and PubChem lists ipamorelin acetate among its synonyms. Counter-ions add weight without adding peptide. The table shows the arithmetic, assuming exactly two counter-ions and no water; real material is described by its certificate.

This is why net peptide content sits below the gross weight of a lyophilised solid, as explained in peptide purity vs net peptide content.

Receptor class at the molecular level

By receptor class, ipamorelin is a ghrelin receptor ligand. The ghrelin receptor, GHS-R1a (growth hormone secretagogue receptor type 1a), is encoded by the GHSR gene and belongs to the G protein-coupled receptor 1 family, the rhodopsin-like class A GPCRs. Its type 1a form is a chain of 366 amino acid residues with the seven transmembrane helices common to all GPCRs.

Ipamorelin is grouped in our catalogue with two analogues of different design: tesamorelin, a forty-four-residue analogue of GHRH, and IGF-1 LR3, an eighty-three-residue recombinant polypeptide. At five residues, ipamorelin is the smallest molecule in that research area by a wide margin.

How ipamorelin is analysed: HPLC and LC-MS

The fragment ions follow the standard b/y naming. b ions contain the N-terminus and y ions the C-terminus. Because ipamorelin ends in an amide, each y ion carries NH2 rather than OH, so the y series sits 0.984 Da lower than it would for the free acid.

Stereochemistry is where chromatography earns its place. Ipamorelin has four stereocentres, at the α-carbons of His, D-2-Nal, D-Phe and Lys, so fifteen other stereoisomers share its formula and mass. A diastereomer with L-Phe in place of D-Phe, or with a racemised histidine, cannot be told apart by mass at all, but it has different physical properties and separates on a reversed-phase column. Histidine is among the residues most prone to racemisation during coupling, which makes that diastereomer one of the first related substances to look for.

More detail on each method is in the guides to HPLC peptide purity and mass spectrometry for peptide identity.

Reading an ipamorelin certificate of analysis

Our ipamorelin is supplied at ≥99% purity (HPLC). When reading any certificate for ipamorelin, check that the sequence is written with the D-prefix on both naphthylalanine and phenylalanine and with Aib at position 1, that the observed mass matches the values above, that the salt form or counter-ion content is stated, that the HPLC method gives its detection wavelength, and that the report carries a batch reference and an analysis date. How to read a peptide certificate of analysis walks through each line of a typical report.

Form and storage of the lyophilised solid

Ipamorelin is supplied as a lyophilised powder in a sealed 10 mg vial. Identifiers, price and availability are listed on the ipamorelin product page.

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. Handle the material as a laboratory chemical, following your institution's chemical-safety procedures. Storing lyophilised peptides explains why cold, dark and dry storage matters for a freeze-dried solid.

In our catalogue, ipamorelin sits in the GHRH, GHS-R & IGF-1 Analogues research area. Chemical terms used on this page, such as D-amino acid, C-terminal amide and monoisotopic mass, are defined in the glossary.