pe
pep-10441 v1 CC-BY-SA-4.0

Bone-and-calcium-signaling peptide (CHEMBL499651)

A short experimental peptide that switches on the body's main parathyroid hormone receptor, which helps control calcium levels and bone strength; experimental, not yet an approved drug.

statusbioassayed targetPTH1R length13 aa refs2
EARLY ENTRY This candidate is newly indexed — supporting evidence is still being added. Have a paper or data point? Contribute below.
status 5 / 5
prediction metrics boltz-2 1.0
ipTM0.747
pTM0.542
avg pLDDT55.3
ranking score0.592
STRUCTURE · PEP-10441 × PTH1R
ranking0.592
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
boltz-2 1.0 · mmCIF ↓ download
sequence13 aa
151013
AVAEIQLHQAKWY
in the news 1 article
Hypotheses2 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

Do the two aromatic amino acids at the very end of this peptide do most of the work of sticking to the bone receptor?

If true, chemists could focus on just those two pieces to build simpler, cheaper, and more stable molecules for future bone drugs, shortening the path to new treatments.

The hypothesis
The C-terminal WY dipeptide of AVAEIQLHQAKWY forms a hydrophobic aromatic anchor that is necessary for PTH1R engagement, such that truncating or substituting these residues abolishes detectable receptor affinity.
Why it’s plausible
Tryptophan and tyrosine are bulky aromatics capable of pi-stacking and cation-pi interactions with receptor residues. In class B GPCRs, C-terminal hydrophobic residues of ligands frequently contribute disproportionately to binding energy. The sequence context here places WY at the extreme C-terminus, maximally exposed, which is consistent with an anchor role. The moderate ipTM of 0.747 implies the interface is real; the most likely structural rationale for a 13-mer achieving this score is a focused hydrophobic contact rather than a distributed polar network.
Why it matters
Identifying WY as a necessary anchor would define a minimal pharmacophore for rational medicinal chemistry, guiding stapled or constrained analogues that preserve the anchor while improving proteolytic stability.
Plausibility.45
Novelty.50
Impact.50
Basis · grounding1 paper · 2 computed/notes
[1]
sequenceWY at positions 12-13 (C-terminus); W and Y are the two most hydrophobic aromatic amino acids and frequently serve as GPCR-ligand anchors
[2]
structureboltz-2 complex ipTM=0.747 is above random-docking noise, suggesting genuine structural contact
[3]
paper
Class B GPCR ligand binding reviews note key roles of C-terminal hydrophobic/aromatic residues in peptide hormones
doi: 10.1124/pr.114.009464
openupdated 2026-06-05

Could connecting the two ends of this peptide into a ring make it bind the bone receptor more tightly and survive longer in the body?

If true, a once-weekly or once-monthly bone drug could replace the daily injections that many osteoporosis patients find burdensome, improving quality of life and treatment success rates.

The hypothesis
Cyclization of AVAEIQLHQAKWY between the Ala1 N-terminus and the Lys11 side-chain amine would constrain the peptide into a helical turn that enhances PTH1R affinity and proteolytic resistance without eliminating receptor recognition.
Why it’s plausible
The sequence EIQLHQAK spans residues 4-11 and has a helical propensity consistent with a single alpha-helical turn. Lys11 is positioned approximately one helical turn from the N-terminus, making a head-to-side-chain lactam cyclization geometrically feasible. Constrained PTH analogues with i to i+7 lactam bridges have shown improved receptor affinity and plasma half-life. The moderate ipTM (0.747) and low pLDDT (55.3) together suggest the linear peptide is conformationally flexible; rigidification by cyclization is predicted to reduce the entropic binding penalty.
Why it matters
A cyclic analogue with enhanced stability could be administered subcutaneously with a longer dosing interval than current daily teriparatide injections, improving patient adherence in the treatment of osteoporosis.
Plausibility.40
Novelty.50
Impact.55
Basis · grounding1 paper · 2 computed/notes
[1]
sequenceK at position 11 and free N-terminus at position 1 provide a chemically accessible i-(i+10) lactam cyclization pair; EIQLHQA segment has alpha-helical propensity
[2]
structurepLDDT=55.3 reflects disordered free peptide; conformational pre-organization via cyclization is a validated strategy to convert disordered peptide binders into higher-affinity constrained leads
[3]
paper
Review covers cyclic and stapled PTH analogues as a design strategy for improved PTH1R ligands
doi: 10.1124/pr.114.009464
details expand to inspect
full evidence table1 metrics
metricvaluetool
IC50 2187 nM GPCRDB/ChEMBL
structural qualityopenfold3
metricvaluenote
gpde2.058global PDE — lower = better
disorderNaNfraction disordered
3-letter notation
Ala-Val-Ala-Glu-Ile-Gln-Leu-His-Gln-Ala-Lys-Trp-Tyr
recipeboltz-2 1.0
parametervalue
modelboltz-2 1.0
weights
hardwarenvidia_nim_api
mlx version
python
random seed
msa strategynone
diffusion samples1
runtime
predicted bymlx@peptide
predicted at2026-04-24
citationbibtex
peptidemodel (2026). Bone-and-calcium-signaling peptide (CHEMBL499651) (pep-10441, v1). PeptideModel. https://peptidemodel.com/card/pep-10441
@peptide{pep10441,
  sequence = {AVAEIQLHQAKWY},
  target   = {pth1r},
  author   = {peptidemodel},
  year     = {2026},
  status   = {bioassayed}
}
related peptides 5 by signal overlap
clinical trials 0 trials · checked 2026-05-22
0
no registered clinical trials as of 2026-05-22; we'll re-check periodically
references 2 papers
discussion no comments
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