CGRP tail fragment: lab research tool (NVGSEAF)
A tiny piece of the CGRP nerve peptide, used in lab studies to understand how CGRP interacts with the calcitonin receptor; not a drug and has no clinical use.
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
What this is
alpha-CGRP (31-37) is a short seven-amino-acid fragment (NVGSEAF) corresponding to the C-terminal tail of rat, mouse, and canine alpha-CGRP — the full neuropeptide that gives the calcitonin/CGRP family its name. It is not a drug and has no clinical use; it is a research peptide used to ask which parts of the parent CGRP molecule do what. The stored sequence is the unmodified linear heptapeptide and represents only the very C-terminus of the 37-residue parent hormone — the rest of the CGRP molecule, including its N-terminal disulfide ring, is not present in this fragment. The "E" at position 36 distinguishes the rat/mouse/canine alpha form from the human beta-CGRP C-terminus, which carries a lysine at the same position.
What it does
In isolation, the heptapeptide is a much weaker pharmacological tool than intact CGRP. Maton and colleagues (1990) tested C-terminal fragments of CGRP on dispersed acini and pancreatic membranes and reported that short CGRP C-terminal peptides behave as agonists at the cholecystokinin (CCK) receptor rather than as functional CGRP receptor agonists — a reminder that fragments of a peptide hormone often acquire activity at unrelated receptors instead of preserving the parent's pharmacology. The platform attaches this card to the calcitonin receptor (calcr) because the parent peptide alpha-CGRP belongs to the calcitonin/CGRP/amylin receptor family (Hay 2018), but the fragment itself has not been shown to be a selective calcitonin-receptor ligand.
Mechanism
The parent peptide alpha-CGRP acts through class B (secretin-family) GPCRs that are reshaped by accessory proteins called RAMPs: the calcitonin receptor-like receptor (CLR) paired with RAMP1 becomes the canonical CGRP receptor, while the calcitonin receptor (CTR) paired with RAMP1/2/3 forms the amylin (AMY) receptors (Hay 2018, Barwell 2012). The C-terminal portion of CGRP — including the region this heptapeptide is taken from — is generally regarded as contributing to receptor recognition and binding in the parent hormone, whereas the N-terminal disulfide-bonded loop is required to drive G-protein activation; RAMPs further reshape ligand selectivity at these receptors as allosteric modulators (Advances in Pharmacology 2020). Because NVGSEAF lacks the disulfide loop and most of the central helical region of CGRP, it would not be expected to act as a full agonist at the CLR/RAMP1 CGRP receptor, which is consistent with the Maton (1990) observation that C-terminal CGRP fragments instead engage the CCK receptor.
Evidence
- Human: No human studies of this fragment.
- Animal/in vitro: Maton and colleagues (1990) reported agonist activity of C-terminal CGRP fragments at the CCK receptor on dispersed pancreatic acini and membranes. Broader pharmacology of the calcitonin/CGRP/amylin receptor family — including the calcitonin receptor that this card is linked to — is reviewed by Hay and colleagues (2018) and by Barwell and colleagues (2012). Mechanistic work on calcitonin/amylin receptor peptide interaction has been carried out by Lee and colleagues (2016), and the role of RAMPs as allosteric modulators of these receptors is reviewed in Advances in Pharmacology (2020). None of these specifically validate NVGSEAF as a calcitonin-receptor ligand; they establish the receptor-family context the parent peptide and its fragments are studied against.
Related peptides
Alpha-CGRP (31-37) is a fragment of the parent peptide alpha-CGRP and shares its receptor-family context with calcitonin, amylin, adrenomedullin, and adrenomedullin-2/intermedin (Hay 2018). These all act through class B GPCRs — the calcitonin receptor (CTR, the target this card is linked to) and the calcitonin receptor-like receptor (CLR) — whose ligand selectivity is reshaped by RAMP1, RAMP2, and RAMP3 accessory proteins (Barwell 2012). The fragment is closest in sequence to the C-terminus of the rat, mouse, and canine alpha-CGRP parent peptide; the equivalent C-terminal region of human beta-CGRP differs by one residue (lysine in place of glutamate at position 36).
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.
Does NVGSEAF actually bind to the calcitonin receptor, or does it instead act on a gut hormone receptor as older experiments suggested?
Getting the target right directs research toward the correct disease areas. If the true target is a gut receptor, this fragment could inform drug development for digestive and metabolic conditions rather than migraine or bone disease.
Does removing the flexible glycine at position 3 prevent this fragment from activating its receptor?
If a single amino acid controls the shape needed for receptor activation, chemists could design rigid versions of this fragment that lock in the active shape, potentially making more potent or selective research tools.
Does the glutamate at position 6 of NVGSEAF explain why rat CGRP fragments activate gut hormone receptors instead of their parent's target?
If true, this tiny peptide could become a clean, non-sulfated research tool for studying gut hormone receptors, which are targets for obesity and digestive disease drugs. It would also explain why rat and human versions of the same fragment behave differently.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.9233613014221191 | boltz-2 |
| ranking score | 0.6771465539932251 | boltz-2 |
▸3-letter notation
▸recipeboltz-2 2.2.1
| parameter | value |
|---|---|
| model | boltz-2 2.2.1 |
| weights | — |
| hardware | vast_v100_32gb |
| mlx version | — |
| python | — |
| random seed | 1 |
| msa strategy | colabfold_local |
| runtime | — |
| predicted by | — |
| predicted at | 2026-05-22 |
▸citationbibtex
@peptide{pep10625,
sequence = {NVGSEAF},
target = {calcr},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}