pe
pep-10560 v1 CC-BY-SA-4.0

Ghrelin hunger hormone: shortened lab fragment (Ghrelin [1-27])

A 27-amino-acid piece of the stomach's hunger hormone ghrelin, used in lab studies to understand how ghrelin activates the brain's hunger receptor; experimental, not yet an approved drug.

statussynthesized targetGHSR length27 aa refs5
snapshot in_vitro 0% confidence
Class
Endogenous peptide fragment (ghrelin-derived)
Status
No approved therapeutic status identified
Best-supported effect
GHS-R activation and intracellular calcium increase in GHS-R-expressing cells (in vitro)
Main caveat
No animal or human efficacy data identified in this card's source file
status 4 / 5
prediction metrics boltz-2 1.0
ipTM0.856
pTM0.910
avg pLDDT83.4
ranking score0.838
STRUCTURE · PEP-10560 × GHSR
ranking0.838
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
boltz-2 1.0 · mmCIF ↓ download
sequence27 aa
151015202527
GSSFLSPEH QRVQQRKES KKPPAKLQP
in the news 1 article
overview readme

Snapshot

Class: Endogenous peptide fragment (ghrelin-derived)
Evidence tier: In vitro / assay evidence
Status: No approved therapeutic status identified
Best-supported effect: GHS-R activation and intracellular calcium increase in GHS-R-expressing cells (in vitro)
Main caveat: No animal or human efficacy data identified


What this is

Ghrelin [1-27] is a 27-amino acid fragment of human ghrelin, an endogenous peptide hormone produced primarily in the stomach. The full-length ghrelin peptide contains 28 residues; the [1-27] form lacks the C-terminal arginine (Arg-28) found in full-length ghrelin. Ghrelin [1-27] was identified during biochemical characterization of ghrelin-derived molecules produced by post-translational processing of the ghrelin precursor.

In cell-based assays, synthetic Ghrelin [1-27] has been shown to activate the growth hormone secretagogue receptor (GHS-R) and induce intracellular calcium increases in GHS-R-expressing cells, a response qualitatively similar to that of full-length ghrelin, decanoyl ghrelin, and decanoyl ghrelin [1-27].


Evidence map

Evidence layerGradeWhat it supports
HumanNone identifiedNo human trial or observational data identifieds available literature
AnimalNone identifiedNo animal study data identifieds available literature
In vitroWeakGHS-R activation and intracellular calcium increase in GHS-R-expressing cells; from a single structural characterization study
ComputationalNone identifiedNo structure prediction or docking data identifieds available literature
MechanismPlausibleGHS-R agonism consistent with parent molecule biology; calcium signaling pathway inferred from receptor class

Claim check

ClaimVerdictEvidence layerConfidence
Activates GHS-R and induces intracellular calcium increaseSupported (in vitro)In vitroLow — single structural characterization study; no independent replication identified in source
Equivalent biological activity to full-length ghrelinWeak (in vitro, partial)In vitroLow — qualitative similarity reported in GHS-R calcium assay; functional equivalence across all ghrelin endpoints not established
Human efficacy for any indicationNot establishedNoneLow — no human data present

Assay conditions

This section reports conditions used in assays. It does not establish animal or human exposure.

ContextSystemAssay conditionTimepointEndpointLimitation
In vitro characterizationCells expressing GHS-RSynthetic Ghrelin [1-27]; exact concentration not individually extracted from sourceNot individually extractedIntracellular calcium increaseSingle study; exact assay concentration, duration, and cell line not individually extracted's available literature

Assay limitations

  • Intracellular calcium response was measured in GHS-R-expressing cell systems; this does not establish in vivo receptor pharmacology, bioavailability, or systemic effect.
  • No animal toxicology or human safety data are identifieds available literature.
  • Published research characterization study was primarily focused on structural identification of ghrelin-derived molecules, not on pharmacological profiling of Ghrelin [1-27] as an isolated therapeutic candidate.
  • In vitro activity in this assay system does not establish systemic tolerability, potency relative to clinical benchmarks, or any human-relevant endpoint.

Mechanism

Ghrelin [1-27] is proposed to act as an agonist at the growth hormone secretagogue receptor (GHS-R), a G protein-coupled receptor expressed in the pituitary and other tissues. GHS-R activation is associated with downstream calcium mobilization via Gq/phospholipase C signaling, which is the basis of the intracellular calcium assay response reported in available literature. This mechanism is inferred from receptor class and parent molecule biology; target specificity relative to full-length ghrelin and potency at GHS-R have not been separately established for Ghrelin [1-27] in the available literature.


Chemistry

FieldValue
Amino-acid chainGSSFLSPEHQRVQQRKESKKPPAKLQP
Full notationH-Gly-Ser-Ser-Phe-Leu-Ser-Pro-Glu-His-Gln-Arg-Val-Gln-Gln-Arg-Lys-Glu-Ser-Lys-Lys-Pro-Pro-Ala-Lys-Leu-Gln-Pro-OH
Length27 amino acids
TopologyLinear
ModificationNone reported; unacylated form (lacks the octanoyl modification present in acyl ghrelin)
Key difference from parentLacks C-terminal Arg-28 of full-length ghrelin
Molecular weightNot individually extracted from available literature
CASNot individually extracted from available literature
Sequence confidenceVerified (matches sequence reported in Hosoda et al. 2003)

Open questions

  • GHS-R potency and selectivity: Relative binding affinity and potency of Ghrelin [1-27] at GHS-R compared with full-length acyl ghrelin and other ghrelin-derived molecules has not been individually characterized in available literature.
  • Animal translation: No animal studies using Ghrelin [1-27] as an isolated compound are identifieds available literature. Whether in vitro GHS-R activity translates to in vivo GH release, appetite, or metabolic endpoints is unknown from available literature.
  • Human translation: No human data of any kind are identifieds available literature.
  • Acylation requirement: Full-length ghrelin requires octanoylation at Ser-3 for high-affinity GHS-R binding; published research does not characterize whether Ghrelin [1-27] (unacylated) retains meaningful GHS-R agonism relative to acyl forms.
  • Physiological role: Whether Ghrelin [1-27] is produced endogenously at biologically significant levels and has a distinct physiological function from full-length ghrelin is not addressed in the available literature.
Hypotheses2 directions▾ collapse

Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.

openupdated 2026-06-11

Does this shortened, unacylated ghrelin fragment only partly activate the hunger receptor instead of fully switching it on?

If Ghrelin [1-27] only weakly activates hunger signaling, it could point toward new ways to study or adjust appetite signaling in obesity research.

The hypothesis
Unacylated Ghrelin [1-27] activates GHSR through a partial agonist mechanism, inducing calcium mobilization but producing submaximal receptor activation compared to octanoyl-ghrelin, because the absence of the Ser3 fatty acid prevents the hydrophobic pocket engagement required for full efficacy.
Why it’s plausible
Full-length ghrelin requires octanoylation at Ser3 for high-potency GHSR activation; unacylated ghrelin (des-acyl ghrelin) is generally considered a weak partial agonist or biased agonist. The [1-27] fragment as described in the readme appears to be unacylated (no mention of acyl modification), and the weak in vitro evidence grade suggests the calcium response may be sub-maximal. A partial agonist mechanism would mean [1-27] could block full agonist signaling at saturating concentrations.
Why it matters
If [1-27] is a natural partial agonist at GHSR, it could serve as an endogenous brake on ghrelin-driven appetite and GH release, representing a novel regulatory mechanism in the ghrelin axis.
Plausibility.62
Novelty.55
Impact.60
Basis · grounding1 paper · 1 computed/note
[1]
noteIn vitro evidence graded 'Weak', activation qualitatively similar but not quantitatively benchmarked against fully acylated ghrelin
[2]
paper
Suppressed ghrelin signaling has beneficial effects on appetite and fat mass, suggesting partial antagonism/partial agonism has physiological consequence
doi: 10.1007/s00726-012-1355-2
openupdated 2026-06-11

If you chemically attach a small fat group at Ser3 of this shorter ghrelin piece, does it become as powerful as the natural hormone?

If yes, it could yield a ghrelin analog that is one residue shorter and potentially simpler to make, which is relevant to treatments for muscle wasting and growth hormone deficiency.

The hypothesis
Introducing a stable octanoyl or palmitoyl group at Ser3 of Ghrelin [1-27] would substantially increase GHSR potency while the [1-27] backbone confers improved synthetic accessibility and peptide stability compared to full acyl-ghrelin [1-28], producing an optimized acylated analog with at least equivalent receptor activity.
Why it’s plausible
Full ghrelin requires octanoylation at Ser3 for high potency; this modification is added enzymatically by MBOAT4. Synthetic acylation of Ser3 in truncated fragments is well established. Since Ghrelin [1-27] already activates GHSR (calcium assay, ipTM 0.856), the backbone is receptor-compatible. The loss of one residue reduces synthesis steps and potential aggregation, and chemical acylation at Ser3 could restore full agonist potency, yielding a simpler, more stable therapeutic candidate than full-length ghrelin.
Why it matters
A 27-residue acylated analog with equivalent potency to 28-residue ghrelin would be easier to manufacture at scale and potentially more metabolically stable, lowering the barrier to clinical development for growth hormone deficiency and cachexia indications.
Plausibility.78
Novelty.30
Impact.55
Basis · grounding1 paper · 2 computed/notes
[1]
sequenceSer3 is present in the [1-27] sequence (GSSFLSP), the canonical acylation site for MBOAT4-mediated octanoylation in full ghrelin
[2]
structureipTM=0.856 confirms the 27-residue backbone forms a competent GHSR-binding conformation, establishing that acylation at Ser3 is the logical potency-boosting modification
[3]
paper
GHS-R activation studied in context of secretagogue analogs, establishing the chemical precedent for GHSR-active acylated ligands
doi: 10.3390/ijms15034837
details expand to inspect
full evidence table2 metrics
metricvaluetool
ipTM 0.8558362126350403 boltz-2
ranking score 0.837988555431366 boltz-2
structural qualityopenfold3
metricvaluenote
gpde0.547global PDE — lower = better
disorderNaNfraction disordered
3-letter notation
Gly-Ser-Ser-Phe-Leu-Ser-Pro-Glu-His-Gln-Arg-Val-Gln-Gln-Arg-Lys-Glu-Ser-Lys-Lys-Pro-Pro-Ala-Lys-Leu-Gln-Pro
recipeboltz-2 1.0
parametervalue
modelboltz-2 1.0
weights
hardwarenvidia_nim_api
mlx version
python
random seed
msa strategynone
diffusion samples1
runtime
predicted bymlx@peptide
predicted at2026-04-24
citationbibtex
peptidemodel (2026). Ghrelin hunger hormone: shortened lab fragment (Ghrelin [1-27]) (pep-10560, v1). PeptideModel. https://peptidemodel.com/card/pep-10560
@peptide{pep10560,
  sequence = {GSSFLSPEHQRVQQRKESKKPPAKLQP},
  target   = {ghsr},
  author   = {peptidemodel},
  year     = {2026},
  status   = {synthesized}
}
related peptides 2 by signal overlap
clinical trials 1193 on ct.gov · 39 on EUCTR · checked 2026-05-09
ct.gov trials 1193
with results 71
EUCTR 39
PubMed RCT 410
by phase
1phase 39no phase
by status
5completed4recruiting1unknown
references 5 papers
discussion no comments
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