CGRP receptor-binding tail peptide
A small piece of a natural body-signal peptide from the calcitonin family, used only as a lab tool to study how these peptides latch onto their receptors.
- Class
- Endogenous peptide fragment (neuroendocrine)
- Status
- No approved therapeutic status identified
- Best-supported effect
- Identified as a putative neuroendocrine regulatory peptide in a peptidomics screen; no validated bioactivity established
- Main caveat
- No functional assay, animal, or human evidence attached to this card
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
VPTNVGSKAF is a 10-residue fragment corresponding to positions 110–119 of the calcitonin gene-related peptide I (CGRP-I) precursor protein — this maps to the C-terminal decapeptide of the 37-amino-acid mature α-CGRP. It belongs to the calcitonin peptide family, which includes calcitonin, α- and β-CGRP, amylin, adrenomedullin, and adrenomedullin 2/intermedin (Hay and colleagues, British Journal of Pharmacology, 2018). The fragment is used primarily as a research tool for probing receptor interactions within this peptide family.
What it does
CGRP-derived fragments interact with receptors of the calcitonin family, principally the calcitonin receptor (CTR/CALCR) and the calcitonin receptor-like receptor (CLR). The intact C-terminal region of CGRP is known to be important for receptor engagement, and isolated C-terminal fragments of CGRP family members have been used in studies of receptor interaction mechanisms (Lee and colleagues, Journal of Biological Chemistry, 2016). The calcitonin receptor itself is expressed on osteoclasts and is progressively upregulated during RANKL-driven osteoclast differentiation (Granholm and colleagues, Journal of Cellular Biochemistry, 2008); it also has biological relevance beyond bone, including roles in the kidney and central nervous system (Pondel, International Journal of Experimental Pathology, 2000).
Evidence
- Human: No clinical data for this isolated fragment.
- Animal: No in vivo data specifically for VPTNVGSKAF.
- In vitro: The fragment corresponds to a region of CGRP identified through peptidomic approaches (Yamaguchi and colleagues, Journal of Biological Chemistry, 2007). Calcitonin and amylin receptor peptide interaction mechanisms — including C-terminal peptide region contributions — have been characterized biochemically at the CALCR level (Lee and colleagues, Journal of Biological Chemistry, 2016).
Mechanism
The calcitonin receptor (CALCR) is a class B GPCR belonging to the secretin receptor family. Its pharmacological diversity arises from heterodimerization with receptor activity-modifying proteins (RAMPs): CTR paired with RAMP1, RAMP2, or RAMP3 forms the amylin receptor subtypes AMY₁, AMY₂, and AMY₃, respectively, which are also activated by amylin and, to varying degrees, by CGRP and adrenomedullin (Hay and colleagues, British Journal of Pharmacology, 2018). CLR paired with RAMP1 forms the canonical CGRP receptor, while CLR/RAMP2 and CLR/RAMP3 form the AM₁ and AM₂ adrenomedullin receptors (Hay and colleagues, 2018). CTR and CLR share structural and signaling themes common to family B GPCRs, with receptor activation engaging both cAMP and intracellular calcium pathways (Barwell and colleagues, British Journal of Pharmacology, 2012). The C-terminal region of calcitonin-family peptides — the region this fragment derives from — contributes to receptor selectivity and binding affinity across the CTR/CLR receptor system (Lee and colleagues, Journal of Biological Chemistry, 2016).
The relevance of this fragment to the amylin receptor system (CTR + RAMPs) makes it useful as a reference sequence when studying co-agonist approaches that engage CTR, such as combination therapies pairing GLP-1 and amylin receptor agonism.
Related peptides
The CGRP-I precursor gives rise to full-length α-CGRP, a major vasodilatory neuropeptide acting at CLR/RAMP1. Other calcitonin-family members that engage overlapping receptor systems include calcitonin (CTR agonist) and amylin (CTR/RAMP complex agonist).
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.
Could this small CGRP piece sit in the calcitonin receptor on osteoclasts and prevent the signals that normally slow down bone breakdown?
If CGRP breakdown products generated naturally in the body antagonize bone-protective calcitonin signaling, this could explain why some people lose bone faster than expected. It might also point to a new way to fine-tune bone metabolism in conditions like osteoporosis.
Does removing the front part of CGRP change which of the four related calcitonin-family receptors the remaining tail prefers to bind?
If the fragment hits different receptor subtypes than full CGRP, scientists could use it to study individual receptor pathways in migraine, blood vessel regulation, or bone disease without disturbing the others, making research faster and more precise.
Does this small CGRP fragment bind the calcitonin receptor specifically, avoiding the CGRP receptor that drives migraine and other effects?
If this fragment is selective for the calcitonin receptor, it could help researchers study bone loss and kidney disease pathways in isolation, without accidentally blocking migraine-related receptors that current drugs target. This could lead to cleaner research tools and more targeted drugs.
If a fatty or polymer chain is attached to the end of this 10-residue peptide, would it stay active in the body long enough to be useful as a research or therapeutic tool?
Long-lasting peptide tools that target this receptor could help researchers track or block bone-loss signaling over extended periods in animal models, accelerating the search for new osteoporosis treatments.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.7701838612556458 | boltz-2 |
| ranking score | 0.6057608127593994 | 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{pep10680,
sequence = {VPTNVGSKAF},
target = {calcr},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}