pe
pep-10352 v1 CC-BY-SA-4.0

Blood-sugar-regulating peptide (CHEMBL1222083)

An experimental short peptide that switches on the body's blood-sugar control system, not an approved drug.

statusbioassayed targetGLP-1R length27 aa refs6
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
ipTM0.917
pTM0.815
avg pLDDT72.7
ranking score0.765
STRUCTURE · PEP-10352 × GLP-1R
ranking0.765
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
boltz-2 1.0 · mmCIF ↓ download
sequence27 aa
151015202527
QGTFTSDYS KYLDGRRAQ DFVQWLMNT
in the news 136 articles
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

Could this peptide do two jobs at the same time, helping the body burn more fat while also controlling blood sugar?

Drugs that activate both the GLP-1 and glucagon pathways are being studied for obesity and fatty liver disease because the combination could burn more energy than either target alone. If this hypothesis holds, a peptide already on the radar for blood sugar control might turn out to be useful for those harder-to-treat conditions too.

The hypothesis
The C-terminal segment AQDFVQWLMNT of pep-10352 confers partial agonist activity at the glucagon receptor (GCGR) in addition to full agonism at GLP-1R, making this peptide a functionally unrecognized GLP-1R/GCGR dual agonist.
Why it’s plausible
Native glucagon shares the N-terminal HSQGTFTSDYS core with GLP-1, and the selectivity between GLP-1R and GCGR is primarily determined by the C-terminal helical domain and the receptor N-terminal extracellular domain (10.1038/sj.bjp.0705120). The C-terminal DFVQWLMNT of pep-10352 contains aromatic (F, W) and hydrophobic (V, L, M) residues at positions that partially mirror the glucagon C-terminal alpha-helix responsible for GCGR engagement. The reference (10.1038/sj.bjp.0705120) explicitly states that divergent C-terminal residues of glucagon vs. GLP-1 determine receptor selectivity through interaction with the receptor N-terminal extracellular domain. pep-10352 has an anomalous C-terminal that neither matches GLP-1 nor glucagon exactly, creating ambiguous selectivity.
Why it matters
GLP-1R/GCGR dual agonism is an active therapeutic frontier for obesity and NAFLD because glucagon receptor engagement increases energy expenditure and hepatic fat oxidation on top of the insulinotropic GLP-1 effect. Identifying pep-10352 as a cryptic dual agonist would expand its therapeutic relevance beyond glycemic control.
Plausibility.47
Novelty.35
Impact.70
Basis · grounding2 papers · 1 computed/note
[1]
paper
GLP-1R N-terminal extracellular domain is the major GLP-1/glucagon selectivity determinant; C-terminal divergence of the ligand determines relative affinity at chimeric receptors
doi: 10.1038/sj.bjp.0705120
[2]
paper
Proglucagon-derived peptides including glucagon, GLP-1, and oxyntomodulin reviewed as therapeutics; overlapping sequence regions support multi-receptor pharmacology
doi: 10.3389/fendo.2021.689678
[3]
sequenceC-terminal DFVQWLMNT contains F, W, L, M hydrophobic residues analogous to glucagon helix residues that contact GCGR transmembrane bundle
openupdated 2026-06-05

Is there a specific spot on this peptide where attaching a fat-like molecule could make it last much longer in the body, the same way it was done to create semaglutide?

Most peptides break down in the bloodstream within hours, which means daily injections. If attaching a fatty acid at the right spot here extends the lifetime to a day or more, it could open a path to a once-weekly GLP-1 drug with a structure different enough from semaglutide to stand on its own scientifically and commercially.

The hypothesis
Fatty acid acylation at K10 of pep-10352 (the lysine in KYLDGRR) would extend plasma half-life to greater than 24 hours while preserving GLP-1R agonism, because K10 is surface-exposed in the receptor-bound conformation predicted by Boltz-2 and is geometrically equivalent to the acylation site used to create semaglutide from liraglutide.
Why it’s plausible
Semaglutide is acylated at K34 of its scaffold (equivalent to K26 in GLP-1 numbering), a site that is solvent-exposed when the peptide is receptor-bound, allowing the fatty acid to extend into solution for albumin binding without sterically disrupting receptor contacts. In pep-10352, K10 sits within the KYLDGRR segment that likely forms the linker turn between the N-terminal activation segment and the C-terminal helix. The high iptm (0.917) suggests this region does not form close receptor contacts, making K10 a candidate acylation site. The axis hit for half-life (10.1038/s42003-025-08249-8) confirms GLP-1-class peptides have a 2-minute native half-life requiring acylation or other modifications for therapeutic use.
Why it matters
If K10 acylation converts pep-10352 into a once-weekly GLP-1R agonist with a distinct C-terminal pharmacophore relative to semaglutide, the compound would occupy a differentiated position in the GLP-1R agonist space without infringing on existing structural patents covering K26/K34 acylation sites.
Plausibility.48
Novelty.12
Impact.52
Basis · grounding1 paper · 2 computed/notes
[1]
paper
Native GLP-1 has 2-minute plasma half-life due to DPP-4 cleavage and renal excretion; acylation for albumin binding is the established strategy for half-life extension
doi: 10.1038/s42003-025-08249-8
[2]
sequenceK10 is the only lysine in the N-terminal half of the peptide; positioned in the KYLDGRR segment structurally between activation segment and C-terminal helix
[3]
structureiptm 0.917 with well-defined interface; K10 region in predicted complex likely occupies a solvent-exposed position compatible with fatty acid extension without disrupting transmembrane contacts
details expand to inspect
full evidence table1 metrics
metricvaluetool
EC50 0.58 nM GPCRDB/ChEMBL
structural qualityopenfold3
metricvaluenote
gpde0.795global PDE — lower = better
disorderNaNfraction disordered
3-letter notation
Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Gly-Arg-Arg-Ala-Gln-Asp-Phe-Val-Gln-Trp-Leu-Met-Asn-Thr
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). Blood-sugar-regulating peptide (CHEMBL1222083) (pep-10352, v1). PeptideModel. https://peptidemodel.com/card/pep-10352
@peptide{pep10352,
  sequence = {QGTFTSDYSKYLDGRRAQDFVQWLMNT},
  target   = {glp-1r},
  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 6 papers
discussion no comments
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