Bone-receptor research fragment (PTHrP 1-16)
A short piece of the natural PTH-related protein, used in labs to study how bone and kidney cells recognize hormones; experimental, not an approved 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
PTHrP(1-16) is the first 16 amino acids of parathyroid hormone-related protein (PTHrP), a hormone that the body makes naturally and that shares its biological "address" — the PTH1 receptor on bone and kidney cells — with the better-known parathyroid hormone (PTH). The full-length PTHrP was originally purified from a human lung cancer cell line, where it was identified as the factor responsible for humoral hypercalcemia of malignancy; the N-terminal region was found to share 8 of its first 16 residues with human PTH, which is why short fragments such as this one are studied as probes of how PTH1R recognizes its ligands (Moseley 1987). The sequence shown here (AVSEHQLLHDKGKSIQ) is identical across human, mouse and rat PTHrP, making it a conserved tool peptide rather than a therapeutic.
History
PTHrP was discovered in the late 1980s as the long-sought tumour-derived factor that drives hypercalcemia in many cancers. Moseley and colleagues (1987) purified an 18 kDa protein from the serum-free medium of the BEN human lung cancer cell line and showed that the first 16 residues were ~50% identical to human PTH, which immediately linked the new factor to PTH-receptor biology. The subsequent two decades clarified that PTHrP and PTH share a common receptor (PTH1R) and that the shortest N-terminal fragments — typically PTH(1-34), PTHrP(1-34) and various truncations — became standard tools for dissecting which residues actually drive receptor activation (Gardella 2015; Sutkeviciute 2019).
What it does
The PTH1 receptor is a class B G-protein-coupled receptor expressed mainly on bone-forming cells (osteoblasts) and on cells of the kidney tubule, where it controls calcium and phosphate handling and remodelling of bone (Lee 2009; Gardella 2015). Full-length PTH and PTHrP, and their 1-34 fragments, activate this receptor strongly. PTHrP(1-16) is a much shorter N-terminal fragment that retains the conserved "address-and-message" sequence shared with PTH but is missing the longer C-terminal portion that is normally needed for a tight, durable interaction with PTH1R — so it is studied as a structural probe of receptor activation rather than as a hormone in its own right (Gardella 2015; Sutkeviciute 2019).
Mechanism
PTH1R adopts two conformations relevant to PTH/PTHrP signaling — an R^G state coupled mainly through Gαs to cAMP, and an R^0 state with longer-lived, internalized signaling — and the choice between them depends on which part of the ligand engages the receptor (Sutkeviciute 2019; Gardella 2015). The first ~14 residues of PTH/PTHrP form the "message" that inserts into the receptor's seven-transmembrane bundle and drives G-protein activation; the residues from ~15 to 34 form the "address" that binds the receptor's extracellular domain and stabilises the complex. PTHrP(1-16) sits almost entirely in the "message" region. Downstream of PTH1R, Gαs/cAMP/PKA signaling in osteoblasts and osteocytes regulates bone formation and resorption, and is itself modulated by cytoskeletal adaptors such as Kindlin-2, whose loss in osteoblast-lineage cells in mice blunts the bone-anabolic response to intermittent PTH (Fu 2020).
Evidence
- Human: No human clinical trials of PTHrP(1-16) itself have been published in the dossier sources. The peptide is used as a research reagent.
- Animal: No animal pharmacology studies of PTHrP(1-16) appear in the dossier sources. Mouse studies in the dossier address PTH1R biology in general — e.g. osteoblast-specific Kindlin-2 deletion blunting intermittent-PTH-induced gains in bone volume and bone mineral density (Fu 2020) — rather than PTHrP(1-16) directly.
- In vitro: The dossier sources describe PTH1R activation by full-length PTH and PTHrP and by their 1-34 fragments (Gardella 2015; Sutkeviciute 2019), but contain no direct biochemical characterisation of PTHrP(1-16) at PTH1R.
Regulatory status
PTHrP(1-16) is a research-grade peptide. It is not an approved drug in the US or EU and is not listed as a therapeutic in the dossier sources. Approved drugs that act on the same receptor (PTH1R) include teriparatide (PTH 1-34) and abaloparatide (a PTHrP analog), but these are separate compounds and are covered on their own cards.
Related peptides
- Parathyroid hormone-related protein (full-length PTHrP) — parent protein from which this fragment is derived.
- Teriparatide (PTH 1-34) — clinically used PTH1R agonist for osteoporosis; shares the conserved N-terminal "message" architecture but contains the additional "address" region.
- Abaloparatide — PTHrP-based analog of the 1-34 region; also a PTH1R agonist used clinically.
Open questions
- Direct potency and efficacy of PTHrP(1-16) at PTH1R have not been characterised in the dossier sources.
- Whether PTHrP(1-16) shows any receptor selectivity or off-target activity (e.g. at non-PTH receptors) is not established in the dossier sources; the current platform subtitle notes "conflicting evidence" for cardiac endothelin (ET-A/ET-B) receptor activity, but the dossier provided here does not contain a primary source for that claim and it should be re-verified before being relied on.
- Structural data on PTHrP(1-16) bound to PTH1R, as distinct from the well-studied 1-34 complexes, are not represented in the dossier sources.
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 fragment naturally prefer the bone receptor over the brain receptor?
If PTHrP(1-16) only hits the bone receptor, researchers could use it to study bone and kidney biology without worrying about unwanted brain effects, and it could be the foundation for cleaner bone drugs.
Could small chemical tweaks at the less-critical spots in this peptide make it last much longer in the body?
If chemical modifications at non-essential positions extend the peptide's survival in the bloodstream without weakening receptor binding, this research fragment could become a candidate for further drug development. Whether binding is actually preserved would still need to be checked, and the exact tolerant positions are not yet pinned down.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.9272828102111816 | boltz-2 |
| ranking score | 0.6010429859161377 | 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{pep10501,
sequence = {AVSEHQLLHDKGKSIQ},
target = {pth1r},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}