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GHRP-2: structure, mechanism and research use

NuVion GHRP-2 research peptide vial

Table of Contents

GHRP-2, also known as pralmorelin, is a synthetic hexapeptide agonist at the growth hormone secretagogue receptor type 1a (GHS-R1a), the receptor whose endogenous ligand is acyl-ghrelin. It belongs to the same D-amino-acid-containing series as GHRP-6 and hexarelin, and it is used as a reference ligand in receptor binding work, Gq signalling assays and pituitary cell culture. NuVion supplies GHRP-2 as a laboratory chemical for in vitro research use only.

Key facts

Type / classSynthetic peptide, growth hormone secretagogue, GHS-R1a agonist
Amino acid count6 residues, C-terminal amide
SequenceD-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH2
Molecular formulaC45H55N9O6
Molecular weight817.98 g/mol (free base)
CAS number158861-67-7
Synonyms / other namesPralmorelin, KP-102, GHRP-2, growth hormone releasing peptide 2
Supplied formLyophilised powder in a sealed vial
NuVion GHRP-2
Available from NuVion

GHRP-2

$79 AUD

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Research use only. Not for human or veterinary use.

Structure and chemistry

GHRP-2 is a linear hexapeptide with three non-standard features: D-alanine at position 1, D-2-naphthylalanine at position 2, D-phenylalanine at position 5, and an amidated C-terminus. Position 2 is where it differs most from its relatives. GHRP-6 carries D-tryptophan there and hexarelin carries D-2-methyl-tryptophan, while GHRP-2 carries the bulkier bicyclic naphthyl side chain. Positions 3, 4 and 6 (Ala, L-Trp, Lys-NH2) are conserved across the series, and the L-Trp at position 4 with the aromatic residue at position 2 forms the two-point aromatic pharmacophore that the receptor’s hydrophobic pocket reads.

Three of the six residues are D-enantiomers. That is a large proportion for a peptide this short and it is the main reason the molecule holds up in serum-containing culture medium, since mammalian aminopeptidases and endopeptidases act on L-configured backbones. Capping the C-terminal lysine as the amide removes the terminal carboxylate and blocks carboxypeptidase action, and it leaves the lysine epsilon-amine as the only ionisable group besides the N-terminal amine, so the peptide carries a net positive charge at neutral pH.

The naphthalene and indole rings dominate the UV spectrum, giving useful absorbance around 280 nm for HPLC quantification, and they also make GHRP-2 markedly more hydrophobic than GHRP-6, so it elutes later on a C18 column under the same gradient. Both ring systems are oxidation-prone under light, and there is no cysteine in the sequence, so the stability considerations are oxidation and photodegradation. GHRP-2 is commonly isolated as an acetate or hydrochloride salt, and the peptide content of a vial is therefore lower than the gross mass, which matters when preparing a stock of defined molarity.

Mechanism of action

GHS-R1a is a class A GPCR found on pituitary somatotroph cells and on hypothalamic neurons. GHRP-2 binds within the transmembrane pocket and stabilises the active receptor conformation, with binding affinity in the low nanomolar range in competition assays against radiolabelled ghrelin analogues. The receptor couples through Gq/11 to phospholipase C-beta, which hydrolyses PIP2 into inositol 1,4,5-trisphosphate and diacylglycerol. IP3 releases calcium from endoplasmic reticulum stores through IP3 receptors, and diacylglycerol together with that calcium activates protein kinase C. In somatotroph cells the rise in cytosolic calcium triggers exocytosis of GH secretory granules, which is measured as GH accumulating in the culture medium.

Across the secretagogue series, the aromatic substitution at position 2 tracks with the concentration-response curve: in pituitary cell culture, GHRP-2 typically produces its half-maximal response at a lower concentration than GHRP-6. Comparing analogues in the same assay on the same day is the standard way to rank them, since absolute values shift with cell preparation and receptor expression level.

Two features of this receptor shape assay design. First, GHS-R1a has high ligand-independent constitutive activity, so a functional assay reads against a substantial baseline and inverse agonists can be detected as a fall below it. Second, agonist binding recruits GRKs and beta-arrestin, which uncouples the receptor from Gq and drives internalisation, giving a second readout that can be compared with the calcium or inositol phosphate signal to describe the coupling profile of a ligand. The receptor is pharmacologically distinct from the GHRH receptor, a class B GPCR coupled to Gs and adenylate cyclase, so a GHS-R1a agonist and a GHRH analogue applied to the same pituitary cells activate two separate second messenger systems, and the combined response exceeds either alone. [D-Lys3]-GHRP-6 is the standard antagonist used to confirm that a response in these systems is GHS-R1a-mediated.

Research applications

GHRP-2 sits in the NuVion Growth Hormones category. Typical study contexts include:

  • Competition binding assays on GHS-R1a membrane preparations or whole cells, ranking affinity against ghrelin, GHRP-6, hexarelin and ipamorelin.
  • Calcium mobilisation assays in GHS-R1a-transfected HEK293 or CHO lines, read on a plate-based fluorescence imaging system.
  • Inositol phosphate accumulation (IP-One HTRF) and PKC translocation assays, quantifying the Gq arm of the pathway and the receptor’s constitutive activity.
  • Beta-arrestin recruitment and receptor internalisation imaging, used to compare coupling profiles across the secretagogue series.
  • Primary pituitary cell culture with GH quantified in the medium by ELISA, alone and in combination with a GHRH receptor agonist.
  • Analytical reference material for LC-MS/MS and RP-HPLC method development, where the naphthylalanine residue gives a distinctive fragmentation pattern.

Handling in the laboratory

GHRP-2 is supplied as a lyophilised powder in a sealed vial. It is reconstituted with bacteriostatic water; the reconstitution calculator gives the volume needed for a target stock concentration. Because the peptide is more hydrophobic than most of its relatives, a brief gentle swirl is sometimes needed for complete dissolution. Keep the sealed vial dry, away from light and refrigerated as described in the product documentation. Keep the reconstituted solution refrigerated and protected from light, and use it within the period stated in the documentation. Aliquoting avoids repeated freeze-thaw cycles, and low-binding labware limits adsorption at nanomolar working concentrations.

The peptide is characterised by RP-HPLC for purity and by mass spectrometry for identity, with the observed protonated ions compared against the calculated mass of the amidated hexapeptide.

Testing and supply from NuVion

NuVion has GHRP-2 independently tested by Janoshik Analytical. Most batches are tested, and the Certificate of Analysis for a tested batch, showing RP-HPLC purity and mass spectrometry identity, is published on the product page and in the Certificates of Analysis library. Manufacture is GMP-audited, the peptide is supplied lyophilised in sealed vials, and orders are dispatched from within Australia.

Related compounds

In the same category, GHRP-6 differs at position 2 and is the usual side-by-side comparator, while Ipamorelin is a selective pentapeptide agonist at the same receptor built on a different scaffold.

Frequently asked questions

What is GHRP-2 used for in research?

It is used as a reference agonist at GHS-R1a. Common work includes competition binding, calcium and inositol phosphate assays in receptor-expressing lines, beta-arrestin recruitment assays, and pituitary cell culture in which GH released into the medium is quantified by ELISA.

How does GHRP-2 differ from GHRP-6?

The two share four of six positions. GHRP-2 has D-Ala at position 1 and D-2-naphthylalanine at position 2, where GHRP-6 has His and D-Trp. The larger aromatic side chain makes GHRP-2 more hydrophobic, changes its retention on a C18 column, and shifts its concentration-response curve to lower concentrations in cell assays.

Is GHRP-2 a therapeutic good in Australia?

No. GHRP-2 is not included in the Australian Register of Therapeutic Goods and has not been assessed by the TGA. NuVion supplies it as a laboratory chemical for in vitro research, and nothing on this page is a representation about therapeutic use.

How should GHRP-2 be stored?

Keep the sealed vial of lyophilised powder dry, away from light and refrigerated as stated in the product documentation. After reconstitution, keep the solution refrigerated and protected from light, and use it within the period the documentation states. Aliquoting avoids repeated freeze-thaw cycles.

Research use only. This product is a laboratory chemical supplied for in vitro research. It is not included in the Australian Register of Therapeutic Goods and has not been assessed by the Therapeutic Goods Administration for quality, safety or efficacy. It is not for human or veterinary use, and nothing on this page is a representation about therapeutic use.

DISCLAIMER

This article is for informational and laboratory-research purposes only. All compounds referenced are supplied strictly for research use and are not for human consumption, diagnosis or treatment.

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