pe
pep-04777 v1 CC-BY-SA-4.0

Blood-pressure-lowering peptide (LAPSTIK)

Blocks ACE, the enzyme that pushes blood pressure up, to help bring it down; experimental, not an approved drug.

statusbioassayed targetACE length7 aa refs2
angiotensin-converting-enzyme-ace-inhibitors
EARLY ENTRY This candidate is newly indexed — supporting evidence is still being added. Have a paper or data point? Contribute below.
status 2 / 5 · 0 verified on platform
prediction metrics boltz-2 1.0
ipTM0.796
pTM0.560
avg pLDDT86.3
ranking score0.849
STRUCTURE · PEP-04777 × ACE
ranking0.849
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
boltz-2 1.0 · mmCIF ↓ download
sequence7 aa
157
LAPSTIK
Hypotheses4 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

Does the last piece of a peptide determine how well it blocks the enzyme that raises blood pressure?

If this holds, it would explain why LAPSTIK is less potent than some other food-derived peptides at blocking ACE, the enzyme that tightens blood vessels. That knowledge could guide researchers to swap one amino acid and make the next insect-protein ingredient significantly more effective for people managing hypertension.

The hypothesis
LAPSTIK inhibits ACE through a binding mode distinct from canonical C-terminal hydrophobic tripeptide inhibitors because its C-terminal residue is the basic Lys rather than the hydrophobic/aromatic residues (Pro, Phe, Trp) that dominate benchmark ACE-inhibitory peptides, leading to weaker S1-pocket engagement and a higher IC50 than insect-derived peptides with hydrophobic C-termini.
Why it’s plausible
ACE's S1 subsite strongly favors hydrophobic or aromatic C-terminal residues; this preference underlies the potency of VPP, IPP, and most food-derived inhibitors. LAPSTIK ends in Lys, a bulky basic residue that would clash electrostatically with ACE's S1 pocket (which contains Glu162 and Glu376). This predicts weaker binding affinity than same-length peptides ending in Pro or Phe, and may shift the binding register toward the S2-S2' sub-pockets where the Pro-3 rigidity and Ile-6 side chain could compensate partially.
Why it matters
Understanding whether C-terminal Lys is penalizing or unexpectedly tolerated clarifies which structural features of insect-derived peptides drive ACE inhibition, directly informing rational sequence engineering to improve potency.
Plausibility.70
Novelty.45
Impact.60
Basis · grounding2 papers · 1 computed/note
[1]
sequenceC-terminal residue is Lys (K); positions 1-6 are LAPSTI, with Pro at position 3 introducing backbone rigidity
[2]
paper
Peptide was identified and bioassayed for ACE inhibitory activity from insect protein digests
doi: 10.1007/s00217-020-03495-y
[3]
paper
Structure-function studies of blood-pressure-lowering peptides show amino acid composition and sequence determine antihypertensive activity
doi: 10.1021/jf5002606
openupdated 2026-06-05

If only the tail end of a peptide does the real work, could you cut it down and keep the benefit?

If true, a stripped-down four-amino-acid version could block the same blood-pressure enzyme at a similar level, and shorter peptides are cheaper to produce and more easily absorbed from food. This could matter for anyone interested in a blood-pressure-supporting functional ingredient derived from insects or other protein sources.

The hypothesis
Truncation of LAPSTIK to the C-terminal tetrapeptide STIK retains the majority of ACE inhibitory activity because the pharmacophore for ACE binding in this sequence resides in the Ser-Thr-Ile-Lys C-terminal segment rather than the Leu-Ala-Pro N-terminal extension, based on the known preference of ACE for recognizing no more than the three to four C-terminal residues of inhibitory peptides.
Why it’s plausible
ACE binds the C-terminal two to four residues of substrates and inhibitors at the primary recognition subsites S1, S1', S2, and S2'. The N-terminal Leu-Ala in LAPSTIK would project away from the active site zinc and contribute mainly to solubility and protease stability rather than binding affinity. The Pro at position 3 is adjacent enough to influence backbone geometry of the C-terminal portion. If ACE's footprint extends only to four residues from the C-terminus (STIK), removing LA would produce a minimal-pharmacophore tetrapeptide with similar or only modestly reduced IC50, while improving synthetic accessibility and cost.
Why it matters
Identifying the minimal binding unit within LAPSTIK would reduce the cost of synthesis, improve oral absorption prospects for smaller peptides, and provide a scaffold for further C-terminal side-chain optimization.
Plausibility.62
Novelty.49
Impact.57
Basis · grounding2 papers · 1 computed/note
[1]
sequenceFull sequence LAPSTIK: positions 1-2 are Leu-Ala (hydrophobic, flexible); position 3 is Pro (rigid); positions 4-7 are STIK (polar-hydrophobic-basic C-terminal tetrapeptide)
[2]
paper
Structure-function studies link amino acid composition and sequence to antihypertensive activity; ACE recognition involves primarily C-terminal residues
doi: 10.1021/jf5002606
[3]
paper
Systolic blood pressure reduction in SHR is documented for ACE-inhibitory peptides administered orally, implying C-terminal binding-competent fragments must survive transit
doi: 10.1016/j.foodchem.2017.02.039
openupdated 2026-06-05

If a peptide was created by stomach-like enzymes in the lab, does that mean it could survive a real stomach?

Most food peptides that look promising in lab tests never reach the bloodstream because stomach and gut enzymes destroy them first. LAPSTIK was discovered precisely by running those same enzymes on insect protein, so it may already be naturally resistant. If that holds up, it could be a rare candidate for a genuine oral functional food ingredient for blood pressure support.

The hypothesis
LAPSTIK survives simulated gastrointestinal digestion with retention of ACE inhibitory activity because it was itself generated by in vitro GI digestion of insect protein, selecting for protease-resistant sequences, and therefore has better oral bioavailability than most exogenously administered food-derived peptides of similar length.
Why it’s plausible
The insect protein digestion protocol used in the discovery papers (10.1111/ijfs.13848; 10.1007/s00217-020-03495-y) mimics gastric and intestinal protease conditions. LAPSTIK emerged intact after this multi-step proteolytic process, which constitutes a functional filter for protease resistance. Peptides that are products of GI digestion rather than survivors despite GI digestion are expected to resist further degradation. This contrasts with peptides identified by in silico digestion that are never tested under GI conditions prior to bioassay.
Why it matters
Demonstrating GI stability would qualify LAPSTIK for serious oral delivery development, distinguishing it from the majority of ACE-inhibitory food peptides that are biologically active in vitro but rapidly degraded before reaching the vasculature.
Plausibility.58
Novelty.46
Impact.63
Basis · grounding3 papers
[1]
paper
LAPSTIK was identified by simulated gastrointestinal digestion (not in silico prediction), meaning it persisted through multi-enzyme proteolytic treatment as an intact bioactive sequence
doi: 10.1111/ijfs.13848
[2]
paper
Low-molecular-weight peptides can retain bioactivity during gastrointestinal digestion; further in vivo evaluation is needed to confirm
doi: 10.1038/s41598-021-84820-7
[3]
paper
ACE-inhibitory peptides must reach the cardiovascular system in active form to exert blood-pressure-lowering; oral survival is the key pharmacokinetic barrier
doi: 10.1079/bjn20041189
openupdated 2026-06-05

Could a single peptide from insect protein help with two of the most common problems in metabolic syndrome?

High blood pressure and type 2 diabetes often come together, and managing both usually means separate drugs or supplements. If LAPSTIK turns out to meaningfully slow the enzyme that drives post-meal blood sugar spikes on top of its blood-pressure effects, it could become a compelling ingredient for functional foods aimed at people dealing with both conditions at once.

The hypothesis
LAPSTIK inhibits alpha-glucosidase with sufficient potency to produce a meaningful reduction in postprandial glucose excursion, making it a dual antihypertensive and antidiabetic food-derived peptide relevant to metabolic syndrome.
Why it’s plausible
The reference paper 10.1007/s00217-020-03495-y explicitly evaluated ACE, alpha-glucosidase, and lipase inhibitory activities in the same insect digest fractions, indicating these assays were run together on the same peptide pool from which LAPSTIK was identified. Lys-containing short peptides have been shown in other food-protein digests to inhibit alpha-glucosidase by blocking the substrate access channel. Hypertension and type 2 diabetes co-occur at high rates; a single peptide acting on both targets would have amplified value as a functional food ingredient.
Why it matters
Dual ACE/alpha-glucosidase inhibition from a single insect-derived heptapeptide would validate a polypharmacological functional food strategy for metabolic syndrome and justify its development as a nutraceutical additive beyond a blood-pressure-only claim.
Plausibility.48
Novelty.52
Impact.68
Basis · grounding1 paper · 1 computed/note
[1]
paper
Study design explicitly evaluated ACE, alpha-glucosidase, and lipase inhibitory activities from the same insect species and digest fractions
doi: 10.1007/s00217-020-03495-y
[2]
sequenceC-terminal Lys and the Ser-Thr dipeptide at positions 4-5 provide polar residues consistent with glucosidase active-site hydrogen-bonding requirements seen in other inhibitory peptides
details expand to inspect
full evidence table2 metrics
metricvaluetool
ipTM 0.7961453795433044 boltz-2
ranking score 0.8494510650634766 boltz-2
structural qualityopenfold3
metricvaluenote
gpde1.305global PDE — lower = better
disorderNaNfraction disordered
3-letter notation
Leu-Ala-Pro-Ser-Thr-Ile-Lys
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-pressure-lowering peptide (LAPSTIK) (pep-04777, v1). PeptideModel. https://peptidemodel.com/card/pep-04777
@peptide{pep04777,
  sequence = {LAPSTIK},
  target   = {ace},
  author   = {peptidemodel},
  year     = {2026},
  status   = {bioassayed}
}
related peptides 5 by signal overlap
references 2 papers
discussion no comments
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