pe
pep-05042 v1 CC-BY-SA-4.0

TIMP2 blood-sugar peptide

An experimental peptide that acts on the body's GLP-1 system, the same pathway that helps control blood sugar and appetite. Not an approved medicine.

statuscomputed targetGLP-1R length40 aa refs2
metabolic
EARLY ENTRY This candidate is newly indexed — supporting evidence is still being added. Have a paper or data point? Contribute below.
status 2 / 5 · 2 contributors
prediction metrics openfold3-mlx 0.3.1
ipTM0.672
pTM0.719
avg pLDDT44.5
ranking score0.746
STRUCTURE · PEP-05042 × GLP-1R
ranking0.746
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
openfold3-mlx 0.3.1 · mmCIF ↓ download
sequence40 aa
1510152025303540
CKITRCPMIPCYISSPDECL WMDWVTEKNINGHQAKFFAC
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 a tiny chemical change stop this peptide from breaking down in the bloodstream within minutes?

Right now this peptide likely falls apart in blood plasma in under ten minutes, making it useless as a medicine even if it works in a test tube. If replacing one vulnerable atom extends that window to over an hour, it could become a realistic candidate for an injectable drug, opening the door to actual animal and human testing.

The hypothesis
Replacing the free (unpaired) C40 in pep-05042 with a non-natural cysteine isostere such as selenocysteine or a thioether-locked analog increases oxidative stability without disrupting the two-disulfide fold, yielding a variant with a serum half-life greater than 60 minutes versus less than 10 minutes for the wild-type peptide.
Why it’s plausible
With five cysteines, pep-05042 almost certainly has one unpaired cysteine (likely C40 at the terminus based on pairing probability). Free thiols in plasma are rapidly oxidized or form mixed disulfides with serum albumin, disrupting the native fold. Replacing C40 with selenocysteine (Se for S swap) preserves hydrogen-bonding geometry and van der Waals contacts while dramatically shifting the reduction potential, making the residue inert to non-specific oxidation. Thioether-locked analogs (lanthipeptide-style) achieve the same end by removing the oxidation-sensitive S-H. The half-life axis hits note that unmodified linear peptides survive only 2-30 minutes in serum; a conformationally locked cystine-knot should substantially exceed this, and removing the reactive free Cys would prevent unfolding.
Why it matters
If pep-05042 has any in vitro activity, its in vivo utility is gated on serum stability. A single-atom substitution at C40 could convert a minutes-half-life molecule to a viable subcutaneous drug candidate, justifying the cost of re-synthesis and enabling the bioassay step that the card currently lacks.
Plausibility.60
Novelty.38
Impact.70
Basis · grounding1 paper · 2 computed/notes
[1]
sourceHalf-life axis hit states that unmodified linear peptides in serum exhibit t1/2 of 2-30 minutes, establishing the stability problem the modification would solve.
[2]
paper
Proteolytic-stability axis hit discusses amino acid substitutions conferring protease resistance, validating the strategy of targeted substitution to extend peptide longevity.
doi: 10.3389/fmicb.2020.563030
[3]
sequenceFive cysteines (odd number) imply one unpaired free Cys at C40 terminus, which is both a liability for oxidative scrambling and the logical engineering target.
openupdated 2026-06-05

Does this peptide lower blood sugar by a different mechanism than currently assumed, one that puts it in the same class as widely used diabetes drugs?

Knowing exactly how a peptide lowers blood sugar determines whether it belongs in a crowded field of GLP-1 drugs like semaglutide or whether it could compete in the well-established gliptin category. If this hypothesis holds, researchers and developers would measure it against a different, already-validated benchmark, which could clarify its real commercial and therapeutic potential.

The hypothesis
pep-05042 inhibits DPP-IV (dipeptidyl peptidase-4) rather than acting through GLP-1 receptor agonism, such that its blood-glucose-lowering effect is mechanistically equivalent to a gliptin, not a GLP-1 mimetic.
Why it’s plausible
The card subtitle attributes activity to the GLP-1 pathway, yet the assigned target is null and the two reference papers focus on dairy-derived ACE and DPP-IV inhibitors. DPP-IV inhibition is the primary mechanism by which food-derived peptides lower blood sugar in vitro, and the references explicitly list DPP-IV as an abbreviation alongside GLP. The sequence contains multiple Pro residues (P7, P10, P16) at positions consistent with DPP-IV substrate/inhibitor motifs, since DPP-IV preferentially cleaves after Pro or Ala at position 2. A peptide rich in these residues can competitively occupy the DPP-IV active site.
Why it matters
Correctly assigning the target determines the entire pharmacological class and competitive landscape. If DPP-IV is the true target rather than GLP-1R, the peptide competes with a validated drug class and its efficacy metrics should be benchmarked against sitagliptin-class inhibitors, not semaglutide-class agonists.
Plausibility.37
Novelty.42
Impact.70
Basis · grounding2 papers · 1 computed/note
[1]
paper
Review explicitly lists DPP-IV and GLP as abbreviations in the context of milk-protein-derived bioactive peptides with metabolic effects.
doi: 10.1007/s13668-023-00472-1
[2]
sequencePro residues at positions 7, 10, and 16 create Pro-X dipeptide motifs relevant to DPP-IV substrate recognition.
[3]
paper
GIP/GLP-1 receptor pharmacology article is cited in axis hits but its relevance is indirect; no direct GLP-1R binding evidence for this peptide exists.
doi: 10.2337/diacare.26.10.2929
details expand to inspect
full evidence table2 metrics
metricvaluetool
ipTM 0.6718364953994751 openfold3-mlx
ranking score 0.7458521127700806 openfold3-mlx
structural qualityopenfold3
0
metricvaluenote
gpde0.823global PDE — lower = better
disorder0.129fraction disordered
chain pair ipTM (A, B)0.672interface quality
3-letter notation
Cys-Lys-Ile-Thr-Arg-Cys-Pro-Met-Ile-Pro-Cys-Tyr-Ile-Ser-Ser-Pro-Asp-Glu-Cys-Leu-Trp-Met-Asp-Trp-Val-Thr-Glu-Lys-Asn-Ile-Asn-Gly-His-Gln-Ala-Lys-Phe-Phe-Ala-Cys
recipeopenfold3-mlx 0.3.1
parametervalue
modelopenfold3-mlx 0.3.1
weights
hardware
mlx version
python
random seed
msa strategy
diffusion samples1
runtime535s
predicted bymlx@peptide
predicted at2026-04-14
citationbibtex
peptidemodel (2026). TIMP2 blood-sugar peptide (pep-05042, v1). PeptideModel. https://peptidemodel.com/card/pep-05042
@peptide{pep05042,
  sequence = {CKITRCPMIPCYISSPDECLWMDWVTEKNINGHQAKFFAC},
  target   = {glp-1r},
  author   = {peptidemodel},
  year     = {2026},
  status   = {computed}
}
related peptides 5 by signal overlap
references 2 papers
discussion no comments
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