pe
pep-10674 v1 CC-BY-SA-4.0

Galanin-27: sheep brain signal peptide used in neuroscience research

A natural sheep nerve-signaling peptide that quiets activity in the brain and spinal cord; used only as a lab research tool to study pain, memory, and mood circuits.

statussynthesized targetGALR1 length27 aa refs7
status 4 / 5
prediction metrics boltz-2 2.2.1
ipTM0.932
pTM0.890
avg pLDDT75.6
ranking score0.791
STRUCTURE · PEP-10674 × GALR1
ranking0.791
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
boltz-2 2.2.1 · mmCIF ↓ download
sequence27 aa
151015202527
TLNSAGYLL GPHAIDNHR SFNDKHGLA
overview readme

What this is

Galanin-27 is a naturally occurring 27-residue fragment of galanin, a neuropeptide found throughout the central and peripheral nervous systems. This particular sequence comes from sheep (Ovis aries) and corresponds to what would be positions 3–29 of the full ovine galanin precursor — it naturally lacks the Gly-Trp dipeptide that opens the sequence in human and rat galanin. Researchers use Galanin-27 as a pharmacological tool to study how galanin's inhibitory signals work in brain regions including the hippocampus, amygdala, and spinal cord, as well as to characterize the binding properties of the three galanin receptor subtypes (GalR1, GalR2, GalR3).

History

Galanin itself was isolated and sequenced in the 1980s from porcine intestinal tissue; the name reflects that the peptide begins with glycine (Gly) and ends with alanine (Ala). Molecular cloning of the human GalR1 receptor was reported by Habert-Ortoli and colleagues in 1994 (PNAS), who isolated the receptor cDNA from a Bowes melanoma cell library and showed that galanin signals through pertussis toxin-sensitive Gi/Go proteins. GalR2 was subsequently cloned and characterized by Wang and colleagues (Journal of Biological Chemistry, 1997), and GalR3 by Smith and colleagues (Journal of Biological Chemistry, 1998). This receptor family framework made species-variant fragments like Galanin-27 useful tools for dissecting subtype selectivity and structure-activity relationships. Norberg and colleagues (Rapid Communications in Mass Spectrometry, 2004) further expanded the picture by identifying a series of naturally occurring modified variants of galanin in porcine upper intestine, including β-aspartyl-shifted and oxidized forms, illustrating the peptide's chemical heterogeneity across tissues and species.

What it does

Galanin-27 acts on galanin receptors — primarily GalR1 — and, like the full-length peptide, exerts inhibitory effects on neuronal activity. In brain circuits, galanin receptor activation generally suppresses excitatory transmission: in the hippocampus this translates to dampening of seizure activity and modulation of memory-related signaling; in the amygdala it influences stress and anxiety-related responses; in the spinal cord it participates in pain modulation. Galanin-27 retains the core pharmacophore needed for receptor engagement and is used experimentally to activate these pathways selectively and to compare receptor binding profiles against other galanin fragments and analogs.

Evidence

  • Human: No clinical trials have been reported for Galanin-27 itself. Research in this area is preclinical.
  • Animal: Galanin receptor pharmacology has been extensively studied in rodent models of epilepsy, pain, cognition, and anxiety. Galanin-27 and related fragments have been used in binding assays and functional studies to characterize receptor subtype contributions (Webling et al., Frontiers in Endocrinology, 2012).
  • In vitro: Binding and functional assays in transfected cell lines have been used to define the receptor selectivity of galanin fragments. Lu and colleagues (Neuropeptides, 2005) demonstrated that the shorter fragment galanin(2–11) binds GalR3 in transfected cells, illustrating how fragment boundaries affect receptor subtype engagement.

Known effects

  • GalR1 agonism — Preclinical; primary pharmacological activity of the fragment (Webling et al. 2012)
  • Inhibition of hippocampal excitability — Preclinical (rodent models); mechanism relevant to seizure research
  • Pain modulation (spinal cord) — Preclinical; galanin receptor activation implicated in nociceptive gating
  • Anxiety and stress circuit modulation (amygdala) — Preclinical; galanin receptor expression in limbic regions

Regulatory status

  • Research use only. Galanin-27 has no approved therapeutic application.
  • No registered clinical trials for this fragment on ClinicalTrials.gov.

Mechanism

Galanin-27 binds to GalR1, a class A G protein-coupled receptor that signals through pertussis toxin-sensitive Gi/Go proteins, as established for the galanin receptor family by Habert-Ortoli and colleagues (1994). Gi coupling leads to inhibition of adenylyl cyclase and reduction of intracellular cAMP, and in neurons also activates inwardly rectifying potassium channels, hyperpolarizing the cell and suppressing firing. The three receptor subtypes — GalR1, GalR2, GalR3 — differ in downstream coupling and tissue distribution, which is why fragments of varying length are used as pharmacological probes: Webling and colleagues (2012) reviewed the receptor-selectivity profiles of the galanin peptide family including species variants and truncated forms. The stored 27-residue sequence TLNSAGYLLGPHAIDNHRSFNDKHGLA corresponds to the sheep galanin sequence and lacks the N-terminal Gly-Trp present in human and most other mammalian galanins; this N-terminal region is not required for GalR1 binding, which is why the fragment retains full affinity at that subtype. Freimann and colleagues (Expert Opinion on Therapeutic Targets, 2015) reviewed galanin receptors as candidates for therapeutic targeting in neurological disease, providing context for why subtype-selective tools like species-variant fragments remain of interest.

Related peptides

  • Galanin(2–11) — the minimal N-terminal fragment retaining GalR binding; shorter pharmacophore useful for subtype discrimination (Lu et al. 2005)
  • Full-length galanin isoforms (29-residue human/rat, 30-residue bovine) share the same receptor family but differ in C-terminal sequence and species-specific residues
Hypotheses1 direction▾ 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

Could this galanin fragment affect feeding circuits where galanin and ghrelin receptors overlap?

Galanin's role in appetite is documented, so a fragment that engages these circuits could offer a research handle where brain and metabolic signaling overlap; note the specific heterodimer mechanism is still speculative and would need direct evidence.

The hypothesis
Galanin-27 modulates ghrelin receptor (GHSR) signaling in the hypothalamus through a heterodimerization-mediated allosteric mechanism, given that galanin receptors co-localize with ghrelin receptors in feeding circuits and galanin-ghrelin receptor interactions have been reported.
Why it’s plausible
The literature snippet (10.3389/fendo.2012.00146) directly mentions interactions with ghrelin receptors as producing physiological effects. GalR1 and GHSR are both Gi-coupled GPCRs expressed in hypothalamic neurons. If Galanin-27 retains sufficient GalR1 potency (ipTM=0.93 supports this), it may indirectly regulate appetite and energy balance through receptor cross-talk rather than just classical neuropeptide neurotransmission.
Why it matters
Establishing that a galanin fragment can engage feeding circuitry via ghrelin receptor cross-talk would open a new mechanistic window on the well-documented but poorly understood role of galanin in appetite regulation and obesity.
Plausibility.45
Novelty.60
Impact.55
Basis · grounding1 paper · 1 computed/note
[1]
paper
Galanin receptor interactions include ghrelin receptors producing unwanted physiological effects, implying galanin/GHSR cross-talk in endocrine circuits
doi: 10.3389/fendo.2012.00146
[2]
structureipTM=0.93 with GalR1 supports retained receptor engagement that could facilitate GalR1/GHSR heterodimer signaling
details expand to inspect
full evidence table2 metrics
metricvaluetool
ipTM 0.9321333169937134 boltz-2
ranking score 0.7911956906318665 boltz-2
3-letter notation
Thr-Leu-Asn-Ser-Ala-Gly-Tyr-Leu-Leu-Gly-Pro-His-Ala-Ile-Asp-Asn-His-Arg-Ser-Phe-Asn-Asp-Lys-His-Gly-Leu-Ala
recipeboltz-2 2.2.1
parametervalue
modelboltz-2 2.2.1
weights
hardwarevast_v100_32gb
mlx version
python
random seed1
msa strategycolabfold_local
runtime
predicted by
predicted at2026-05-22
citationbibtex
peptidemodel (2026). Galanin-27: sheep brain signal peptide used in neuroscience research (pep-10674, v1). PeptideModel. https://peptidemodel.com/card/pep-10674
@peptide{pep10674,
  sequence = {TLNSAGYLLGPHAIDNHRSFNDKHGLA},
  target   = {galr1},
  author   = {peptidemodel},
  year     = {2026},
  status   = {synthesized}
}
related peptides 5 by signal overlap
clinical trials 0 trials · checked 2026-05-09
0
no registered clinical trials as of 2026-05-09; we'll re-check periodically
references 7 papers
[1]
Identification of variant forms of the neuroendocrine peptide galanin
Norberg, Å. et al. Rapid Communications in Mass Spectrometry 2004
evidence
[2]
Galanin Receptors and Ligands
Webling, K. et al. Frontiers in Endocrinology 2012
supporting
[3] supporting
[5]
Cloned Human and Rat Galanin GALR3 Receptors
Smith, K. et al. Journal of Biological Chemistry 1998
supporting
[6]
Galanin receptors as a potential target for neurological disease
Freimann, K. et al. Expert Opinion on Therapeutic Targets 2015
supporting
[7]
Molecular cloning of a functional human galanin receptor.
Habert-Ortoli, E. et al. Proceedings of the National Academy of Sciences 1994
supporting
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