pe
pep-10652 v1 CC-BY-SA-4.0

Bone-receptor research tool (pTH 3-34, bovine)

A lab-made fragment of cow parathyroid hormone that blocks the bone-regulating receptor without triggering its signal, used only as a lab research tool.

statusbioassayed targetPTH1R length32 aa refs1
EARLY ENTRY This candidate is newly indexed — supporting evidence is still being added. Have a paper or data point? Contribute below.
status 4 / 5 · 2 verified on platform
prediction metrics boltz-2 2.2.1
ipTM0.919
pTM0.787
avg pLDDT60.7
ranking score0.669
STRUCTURE · PEP-10652 × PTH1R
ranking0.669
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
boltz-2 2.2.1 · mmCIF ↓ download
sequence32 aa
15101520253032
SEIQFMHNLGKHLSSM ERVEWLRKKLQDVHNF
in the news 1 article
Hypotheses3 directions▾ 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 2026-06-05

Could adding a molecular crosslink to this peptide stop it from being broken down before it reaches bone cells?

If so, this could lead to an injectable drug candidate that precisely dials down the bone-hormone receptor, helping patients whose PTH signaling is overactive, such as those with parathyroid tumors or chronic kidney disease.

The hypothesis
Introducing a lactam bridge or staple between residues at positions i and i+4 within the predicted C-terminal helix of pTH 3-34 will increase proteolytic stability without compromising the high-affinity PTH1R binding pose, yielding a metabolically stable PTH1R antagonist scaffold.
Why it’s plausible
Unmodified linear PTH fragments are rapidly degraded by serum and tissue proteases. Helix-stapled PTH analogs have been explored for PTH1R agonism; the same approach applied to an antagonist scaffold (3-34) would extend half-life while preserving the documented high-confidence receptor interface. The predicted amphipathic helix in the C-terminal half is the natural stapling target.
Why it matters
A proteolytically stable PTH1R antagonist could be a first-in-class tool for in vivo bone biology studies and a starting point for hypercalcemia or hyperparathyroidism therapeutics.
Plausibility.70
Novelty.45
Impact.60
Basis · grounding2 computed/notes
[1]
structureipTM=0.919 provides a structural model of the receptor-bound helix that can guide staple placement at solvent-exposed, non-contact positions
[2]
sequenceC-terminal segment WLRKKLQDVHNF has i, i+4 pairs (e.g., W17-K21, K21-Q25) suitable for hydrocarbon or lactam stapling without disrupting hydrophobic face contacts
openupdated 2026-06-05

Could blocking the bone-hormone receptor specifically in the kidney help prevent the phosphate imbalance that damages hearts in kidney disease?

If true, this approach could protect heart and blood-vessel health in the millions of people living with chronic kidney disease, without disrupting the bone-building effects they may still need.

The hypothesis
pTH 3-34 acts as a functional antagonist at PTH1R expressed on proximal tubule cells, and could suppress PTH-driven urinary phosphate wasting independently of its skeletal effects, offering a selective renal handle that full-length PTH analogs lack.
Why it’s plausible
PTH1R in the kidney mediates phosphaturia and calcium reabsorption; excessive PTH activity in CKD and hyperparathyroidism drives phosphate wasting. A fragment that blocks the receptor in the tubule without agonism would not trigger the anabolic bone effects of full PTH, producing a kidney-selective pharmacological effect. The lack of N-terminal activation residues makes antagonism at renal PTH1R plausible.
Why it matters
Hyperphosphatemia in CKD is a major driver of cardiovascular mortality. A PTH1R antagonist that corrects tubular phosphate handling without altering bone turnover would address an unmet therapeutic need.
Plausibility.55
Novelty.55
Impact.70
Basis · grounding1 paper · 1 computed/note
[1]
sequenceAbsence of His1-Ser2 removes the primary adenylyl cyclase activation pharmacophore, predicting antagonism over agonism at renal PTH1R
[2]
paper
PTH1R review context covers renal as well as skeletal PTH1R biology; the receptor is expressed in proximal tubule and mediates phosphaturia
doi: 10.1124/pr.114.009464
openupdated 2026-06-05

Do the small differences between bovine and human PTH fragments change which of the two PTH receptors this peptide prefers?

Identifying such a difference would give scientists a cleaner tool to study the second PTH receptor, which is poorly understood but may play roles in brain and reproductive health.

The hypothesis
The bovine-specific residues in pTH 3-34 (relative to human PTH 3-34) confer measurably different affinity for human PTH1R versus PTH2R, revealing which receptor positions discriminate between the two receptor subtypes.
Why it’s plausible
Bovine PTH differs from human PTH at several positions in the 1-34 region. Because pTH 3-34 eliminates the N-terminal activation segment, residue differences in the 3-34 region are fully exposed to receptor contacts. PTH2R does not respond to PTH in the same way as PTH1R; comparing bovine 3-34 affinity at both receptors would map the subtype-discriminating pharmacophore without the confound of agonist-driven internalization.
Why it matters
PTH2R is expressed in brain and testis with poorly understood physiology. A bovine PTH fragment with divergent subtype selectivity would be a valuable tool for dissecting PTH2R biology.
Plausibility.60
Novelty.55
Impact.55
Basis · grounding1 paper · 1 computed/note
[1]
sequenceFull 32-aa backbone SEIQFMHNLGKHLSSMERVEWLRKKLQDVHNF examined; bovine-specific positions can be identified by alignment with human PTH 3-34
[2]
paper
Review covers PTH1R and PTH2R pharmacology at institutions specializing in GPCR biology, establishing the receptor-subtype selectivity question as live and unsolved
doi: 10.1124/pr.114.009464
details expand to inspect
full evidence table2 metrics
metricvaluetool
ipTM 0.918671727180481 boltz-2
ranking score 0.6693214774131775 boltz-2
3-letter notation
Ser-Glu-Ile-Gln-Phe-Met-His-Asn-Leu-Gly-Lys-His-Leu-Ser-Ser-Met-Glu-Arg-Val-Glu-Trp-Leu-Arg-Lys-Lys-Leu-Gln-Asp-Val-His-Asn-Phe
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). Bone-receptor research tool (pTH 3-34, bovine) (pep-10652, v1). PeptideModel. https://peptidemodel.com/card/pep-10652
@peptide{pep10652,
  sequence = {SEIQFMHNLGKHLSSMERVEWLRKKLQDVHNF},
  target   = {pth1r},
  author   = {peptidemodel},
  year     = {2026},
  status   = {bioassayed}
}
related peptides 5 by signal overlap
clinical trials 326 on ct.gov · 14 on EUCTR · checked 2026-05-22
ct.gov trials 326
with results 91
EUCTR 14
by phase
4phase 22phase 44no phase
by status
5completed1active3terminated1unknown
references 1 papers
discussion no comments
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