Calcitonin-related peptide fragment (alpha-CGRP 23-37)
A lab-made piece of a natural nerve-signaling protein, used as a research tool to study pain and blood-vessel pathways by occupying the receptor without fully switching it on. Not a drug.
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
α-CGRP (23–37) is a 15-amino-acid fragment of human α-calcitonin gene-related peptide (α-CGRP), corresponding to the C-terminal portion of the full 37-residue hormone. The stored sequence VKNNFVPTNVGSKAF is the bare backbone — the native full-length α-CGRP is amidated at its C-terminus and disulfide-bridged between Cys2 and Cys7 (neither feature applies to this truncated fragment, which is missing both Cys residues). It is studied as a pharmacological tool peptide rather than a drug: short C-terminal fragments of CGRP can occupy the receptor without triggering full activation, making them useful probes of how the CGRP system signals.
History
The pharmacology of CGRP C-terminal fragments was characterised by Rovero and colleagues in 1992, who reported that both α-CGRP(23–37) and α-CGRP(19–37) behave as antagonists of CGRP at peripheral tissue preparations (Rovero 1992). Their work helped establish that the C-terminal region of CGRP is sufficient for receptor binding, while the N-terminal disulfide-looped region is required for receptor activation — a structure/activity logic that later guided design of clinical CGRP-pathway drugs.
What it does
In tissue assays, α-CGRP(23–37) competes with full-length α-CGRP at its receptor and blocks CGRP-mediated responses without producing a CGRP-like effect of its own (Rovero 1992). It is a "truncation antagonist" — the same C-terminal binding determinants are present, but the N-terminal activation domain has been removed. The peptide is not a therapeutic; it is used in laboratory studies that need a peptide-based CGRP blocker.
Mechanism
CGRP signals through a heterodimeric receptor consisting of the calcitonin receptor-like receptor (CLR) paired with receptor activity-modifying protein 1 (RAMP1); this is one of several receptors built by combining CLR or the calcitonin receptor (CTR) with different RAMPs to produce the CGRP, adrenomedullin (AM₁, AM₂) and amylin (AMY₁, AMY₂, AMY₃) receptors (Hay 2018, Barwell 2012). CTR and CLR are class B (secretin-family) G protein-coupled receptors, and their pharmacology is dictated by which RAMP partner is co-expressed (Barwell 2012). The two-domain binding model for this family — C-terminal peptide region docking to the receptor extracellular domain, N-terminal region engaging the transmembrane bundle to drive activation — predicts that a C-terminal fragment like CGRP(23–37) retains binding affinity but cannot trigger the conformational change needed for G-protein coupling, which matches the antagonist behaviour observed by Rovero and colleagues (Rovero 1992, Lee 2016).
The platform target for this card is the calcitonin receptor (CTR/calcr). Because CTR partners with RAMPs to form amylin receptors, peptides that interact at the CTR-RAMP interface are also of interest for probing amylin pharmacology (Hay 2018, Lee 2016). The selectivity profile of α-CGRP(23–37) across CGRP, AMY and CTR receptors specifically is not detailed in the cited literature.
Evidence
- Human: No human trials. This is a tool peptide, not a clinical candidate.
- Animal/tissue: Antagonism of CGRP-mediated responses by α-CGRP(23–37) and α-CGRP(19–37) characterised in isolated tissue preparations (Rovero 1992).
- In vitro / mechanism: Review-level coverage of how peptides in the calcitonin/CGRP family dock to CTR- and CLR-based receptors, including the role of RAMPs (Hay 2018, Barwell 2012, Lee 2016). Structure/function work on calcitonin analogues at a constitutively active CTR informs the same activation logic (Pozvek 1997). Expression of CTR, CLR and RAMPs during osteoclast differentiation has been mapped in mouse bone marrow macrophages, where RANKL induction shifts the CTR/CLR/RAMP profile (Granholm 2008).
Related peptides
- α-CGRP itself and the related peptides amylin, adrenomedullin and calcitonin all signal through CTR- or CLR-based receptors paired with RAMPs (Hay 2018).
Regulatory status
Not a regulated drug; used as a research reagent. No FDA, EMA or WADA listing applies to this fragment specifically.
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 removing the front of CGRP make what remains bind preferentially to the calcitonin receptor on bone cells rather than the CGRP receptor that controls blood vessels and migraine?
A CGRP fragment that targets the calcitonin receptor specifically could be developed into a bone drug that works without affecting the CGRP pathway that anti-migraine drugs rely on, avoiding potential interference for the many patients who need both migraine treatment and bone protection.
Would replacing two specific amino acids in this CGRP fragment with their chemically mirrored versions make the fragment survive in the body long enough to block the calcitonin receptor in living animals?
CGRP fragments break down too fast to be useful drugs, but changing just a couple of amino acids to their mirror forms could extend their lifespan dramatically. This simple modification could transform a fragile research tool into a practical drug candidate for osteoporosis or bone cancer pain.
Do natural CGRP breakdown products compete with calcitonin on bone-dissolving cells, and does this reduce the bone-protective effect of calcitonin?
If CGRP fragments naturally blunt calcitonin's bone-protective action, this could explain why some people with high sensory nerve CGRP activity have unexpectedly poor bone quality. It might also explain variable responses to calcitonin-based osteoporosis treatments and suggest new ways to improve them.
Does the double-asparagine sequence in this CGRP fragment cause it to form a small structured loop that makes it bind the calcitonin receptor more effectively than a completely floppy peptide would?
If this fragment naturally folds into a small defined shape, chemists could lock that shape permanently using chemical staples, potentially creating a more potent and stable calcitonin receptor drug candidate for osteoporosis treatment.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.8067508339881897 | openfold3-mlx |
| ranking score | 0.8954617977142334 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.730 | global PDE — lower = better |
| disorder | 0.217 | fraction disordered |
| chain pair ipTM (A, B) | 0.807 | interface quality |
▸3-letter notation
▸recipeopenfold3-mlx 0.3.1
| parameter | value |
|---|---|
| model | openfold3-mlx 0.3.1 |
| weights | aedd8f3eb814e392… |
| hardware | apple_m4_base_16gb |
| mlx version | 0.31.1 |
| python | 3.14.3 |
| random seed | 42 |
| msa strategy | colabfold |
| diffusion samples | 1 |
| runtime | 418s |
| predicted by | mlx@peptide |
| predicted at | 2026-04-24 |
python3 openfold3/run_openfold.py predict --query_json {query.json} --runner_yaml examples/example_runner_yamls/mlx_runner.yml --output_dir {output_dir} --num_diffusion_samples 1 ▸citationbibtex
@peptide{pep10677,
sequence = {VKNNFVPTNVGSKAF},
target = {calcr},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}