GHRP-2 Peptide

GHRP-2 (Growth Hormone Releasing Peptide-2, Pralmorelin) is a synthetic hexapeptide (D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH2) and one of the most potent growth hormone secretagogues in its class. It activates the GHS-R1a (ghrelin) receptor with high affinity. Published research has documented GHRP-2 as the most potent GHRP analog for GH release on a per-dose basis. It has been studied as a diagnostic tool for GH deficiency assessment due to its reliable and reproducible GH-releasing activity. For laboratory research use only.

GHRP-2 (Pralmorelin; D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH2) is a synthetic hexapeptide secretagogue that activates the growth hormone secretagogue receptor type 1a (GHS-R1a), the endogenous receptor for ghrelin. By binding this G-protein coupled receptor, GHRP-2 initiates a cascade of intracellular signaling events that converge on growth hormone (GH) release from anterior pituitary somatotrophs, while also engaging hypothalamic circuits that regulate appetite and energy homeostasis.¹

GHS-R1a Receptor Activation

GHS-R1a is a Gq-coupled receptor predominantly expressed in the pituitary and hypothalamic arcuate nucleus. GHRP-2 binds with high affinity, reported in the low nanomolar range (Ki ~1-3 nM in receptor binding assays), and demonstrates greater intrinsic activity at the receptor than first-generation GHRP-6. Receptor activation triggers phospholipase C (PLC) hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 mobilizes intracellular calcium stores while DAG activates protein kinase C (PKC), together producing rapid depolarization of somatotroph membranes and exocytotic release of GH-containing secretory vesicles.²

Synergy with Growth Hormone Releasing Hormone (GHRH)

GHRP-2 does not act on the GHRH receptor; rather, the two pathways are complementary. GHRH stimulates cAMP/PKA signaling in somatotrophs, whereas GHRP-2 stimulates the PLC/IP3/Ca2+ pathway. When administered together in research models, GHRH and GHRP-2 produce a synergistic GH release that exceeds the additive effect of either compound alone. This dual-pathway activation underpins the use of GHRP-2 in combination protocols studied in published clinical research on GH-deficient cohorts.

Somatostatin Antagonism

In addition to direct somatotroph activation, GHRP-2 functionally antagonizes the inhibitory tone of somatostatin (SST) at the pituitary level. Research suggests this disinhibition allows for amplified GH pulses even when endogenous SST tone is elevated, such as during the post-prandial state or in older subjects with declining endogenous GH secretion.

Hypothalamic and Orexigenic Effects

GHRP-2 crosses the blood-brain barrier in limited quantities and stimulates GHS-R1a expressed on neuropeptide Y (NPY) and agouti-related peptide (AgRP) neurons of the arcuate nucleus. In preclinical models this orexigenic signaling has been associated with measurable increases in food intake, paralleling the activity of endogenous ghrelin. The magnitude of the appetite effect is generally lower than ghrelin itself due to GHRP-2's shorter plasma half-life (~15-30 minutes).¹

Downstream Endocrine Effects

Pulsatile GH release driven by GHRP-2 leads to hepatic IGF-1 production via JAK2/STAT5 signaling at the hepatocyte GH receptor. Research literature has documented dose-dependent rises in serum IGF-1 following repeated GHRP-2 administration in preclinical and clinical investigations, with minimal effects on cortisol or prolactin at standard research doses—a selectivity advantage relative to GHRP-6 and hexarelin noted in comparative studies.

The following chemical and physical specifications for GHRP-2 are verified against published peptide chemistry references and PubChem database entries. These properties guide reconstitution calculations, storage decisions, and analytical characterization in research settings.

Full Name	Growth Hormone Releasing Peptide-2 (GHRP-2)
Synonyms	Pralmorelin, KP-102, GPA-748
Molecular Formula	C₄₅H₅₅N₉O₆
Molecular Weight	817.98 g/mol
CAS Number	158861-67-7
Sequence	D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH₂
Amino Acid Count	6 (hexapeptide)
Key Modifications	D-amino acid substitutions at positions 1, 2, and 5; C-terminal amidation; unnatural 2-naphthylalanine at position 2
Origin / Developer	Developed by Cyril Y. Bowers and Tulane University collaborators in the early 1990s as a second-generation synthetic GH secretagogue
Receptor Target	Growth hormone secretagogue receptor 1a (GHS-R1a; ghrelin receptor)
Physical Form	Lyophilized white to off-white powder
Solubility	Soluble in bacteriostatic water, sterile water, and 0.9% sodium chloride. Limited solubility in DMSO. Recommended working solutions at 1-5 mg/mL.
Purity	≥98% by HPLC
Counterion	Typically supplied as acetate salt
Plasma Half-Life	~15-30 minutes (research literature)
Storage	Lyophilized: -20°C long-term. Reconstituted: 2-8°C, use within 14-28 days.

The D-amino acid substitutions at positions 1, 2, and 5 confer significant proteolytic resistance compared to native L-amino acid sequences, contributing to GHRP-2's improved metabolic stability over endogenous ghrelin fragments. The C-terminal amidation prevents carboxypeptidase degradation, and the unnatural 2-naphthylalanine residue is a critical pharmacophore for high-affinity GHS-R1a binding. These structural features collectively underpin the compound's potency profile observed in published binding and functional assays.

GHRP-2 is supplied as a sterile lyophilized powder and requires careful reconstitution to preserve hexapeptide integrity. The compound is generally stable to standard laboratory handling, but contains aromatic residues (D-2-methyl-Trp, D-Phe) susceptible to oxidative and photolytic degradation when in solution.

Recommended Reconstitution Protocol:

1. Equilibrate the vial: Allow the sealed lyophilized vial to reach room temperature (15-20 minutes) before opening to prevent condensation on the powder.
2. Select diluent: Bacteriostatic water for injection (0.9% benzyl alcohol) is the standard diluent for multi-dose research applications. Sterile water for injection may be used for single-use preparations.
3. Calculate concentration: For a 5 mg vial reconstituted with 2 mL of diluent, the working concentration is 2.5 mg/mL (2,500 mcg/mL). Adjust diluent volume to achieve the concentration appropriate for the research protocol.
4. Inject diluent slowly: Direct the stream of diluent down the inner wall of the vial rather than directly onto the lyophilized powder. This minimizes peptide aggregation and foaming.
5. Dissolve gently: Allow the powder to dissolve passively for 30-60 seconds. If undissolved material remains, swirl the vial gently in a circular motion. Do NOT shake or vortex — mechanical agitation introduces shear stress that can fragment the peptide backbone and denature secondary structure.
6. Inspect the solution: The reconstituted solution should be clear and colorless. Discard if cloudy, discolored, or containing particulates.

Compound-Specific Handling Notes:

• Protect from light: The D-2-methyl-Trp residue is photosensitive. Store reconstituted vials wrapped in foil or in opaque containers.
• Avoid repeated freeze-thaw: If aliquoting reconstituted solution for long-term storage, prepare single-use aliquots to avoid degradation from repeated temperature cycling.
• Use low-binding labware: Hexapeptides can adsorb to standard polypropylene at low concentrations; use low-binding tubes when preparing dilute working solutions below 100 μg/mL.
• Sterile technique: Wipe the rubber stopper with 70% isopropanol before each puncture and use a fresh sterile needle for each withdrawal to prevent microbial contamination.

For Research Use Only. GHRP-2 is sold for in vitro and laboratory research applications. This product is not intended for human consumption, diagnostic use, or therapeutic administration.

Proper storage is essential for preserving the structural integrity and biological activity of GHRP-2 across the duration of a research program. The hexapeptide is generally stable under standard cold-chain conditions, but stability differs significantly between the lyophilized and reconstituted states.

Lyophilized Powder Storage:

• Long-term storage: Store sealed lyophilized vials at -20°C in a frost-free freezer. Under these conditions, GHRP-2 retains ≥98% purity for a minimum of 24 months from date of synthesis.
• Short-term storage: Refrigeration at 2-8°C is acceptable for up to 30 days prior to reconstitution.
• Transit conditions: The lyophilized form tolerates brief exposure (≤7 days) to ambient temperatures (15-25°C) during shipping without measurable degradation, consistent with shelf-stability data for related GHS hexapeptides.
• Protect from light and moisture: Keep vials in original sealed packaging until use. Desiccant should remain in shipping containers during storage.

Reconstituted Solution Storage:

• Refrigerated: Once reconstituted, store the solution at 2-8°C. When prepared with bacteriostatic water, the solution remains stable for up to 28 days. When prepared with sterile water, use within 24-48 hours.
• Frozen aliquots: For storage beyond 28 days, divide the reconstituted solution into single-use aliquots and freeze at -20°C or below. Avoid repeated freeze-thaw cycles, which accelerate peptide degradation.
• Do not store at room temperature once reconstituted; aqueous solutions are susceptible to oxidative degradation and microbial growth.

Compound-Specific Stability Considerations:

• Photosensitivity: The D-2-methyl-Trp residue is susceptible to photo-oxidation. Always protect both lyophilized and reconstituted material from direct light.
• No disulfide bonds: Unlike cyclic peptides such as Hexarelin variants, GHRP-2 is a linear hexapeptide without disulfide bridges, which simplifies handling but does not eliminate susceptibility to backbone hydrolysis at pH extremes.
• pH stability: Optimal stability is maintained at neutral pH (6.5-7.5). Avoid exposure to strongly acidic or alkaline conditions.

Adherence to these storage parameters supports reproducible experimental outcomes across longitudinal research studies.