pe
pep-05243 v1 CC-BY-SA-4.0

Experimental anticancer peptide

A lab-studied peptide that researchers are exploring for its potential to fight cancer cells; experimental, not an approved drug.

statusbioassayed targetANTICANCER length55 aa refs3
anticancer
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 2.2.1
ipTM0.000
pTM0.321
avg pLDDT47.2
ranking score0.442
STRUCTURE · PEP-05243 × ANTICANCER
ranking0.442
?
RECEPTOR UNKNOWN
peptide conformation only · no target structure
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
sequence55 aa
1510152025303540455055
GCVWPDGKAIT THKLQTTMLET KALIMGYFKSI ATGGAMMAKPQ EQLTPVIYPAV
in the news 27 articles
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 this molecule kill cancer cells by physically ripping apart their surface, rather than by blocking a protein signal?

If true, cancer cells could not become resistant by simply switching off a receptor, because the attack would be physical, not chemical. This could matter for patients whose tumours have stopped responding to drugs that target specific proteins.

The hypothesis
pep-05243 exerts its anticancer activity primarily through direct disruption of the cancer cell plasma membrane rather than through receptor-mediated signaling, driven by the amphipathic character of its sequence and the strongly hydrophobic C-terminal PVIYPAV segment.
Why it’s plausible
The sequence carries distinct amphipathic architecture: a hydrophilic mid-region (HKLQTTMLETK) flanked by hydrophobic clusters at both termini (GCVWP at the N-terminus and PVIYPAV at the C-terminus). The PVIYPAV stretch is proline-capped, a geometry that resists alpha-helical folding and tends to adopt a beta-turn or extended conformation that inserts efficiently into lipid bilayers. Cancer cells overexpress phosphatidylserine on their outer leaflet, creating an anionic surface that is preferentially targeted by peptides with even modest net positive charge. The peptide has several K and H residues providing positive charge at physiological pH. A membrane-lytic or membrane-perturbing mode would explain anticancer activity in the absence of any annotated receptor target.
Why it matters
Distinguishing membrane disruption from receptor engagement is critical for understanding whether resistance to pep-05243 can emerge (receptor downregulation would not rescue cells) and for predicting selectivity against normal versus malignant cells.
Plausibility.73
Novelty.22
Impact.73
Basis · grounding3 papers · 1 computed/note
[1]
sequenceC-terminal PVIYPAV is strongly hydrophobic and proline-flanked; mid-region HKLQTTMLETK provides polar/positive patch consistent with amphipathic topology
[2]
paper
Hydrophobicity of anticancer peptides plays a crucial role in mechanism of action against cancer cells
doi: 10.1158/1535-7163.mct-10-0811
[3]
paper
Cationic anticancer peptides with high cancer-cell specificity versus normal cells inhibit tumor growth, consistent with membrane-charge-based selectivity
doi: 10.1074/jbc.m111.279281
[4]
paper
Membrane receptor involvement and anti-angiogenesis activities identified as underexplored modes for food-derived anticancer peptides
doi: 10.1016/j.foodchem.2017.10.087
openupdated 2026-06-05

If we trim the peptide down to its most essential piece, would it still kill cancer cells, and could it be made reliably at reasonable cost?

Long peptides are expensive and tricky to produce as medicines. If a short 15-piece fragment works just as well, it could clear a major manufacturing hurdle and bring a usable drug candidate much closer to clinical testing.

The hypothesis
Truncating pep-05243 to the C-terminal 15-residue segment (KPQEQLTPVIYPAV) retains the core anticancer activity of the full-length peptide while reducing the sequence to a length tractable for cost-effective solid-phase synthesis and improved proteolytic stability, because the PVIYPAV hydrophobic anchor together with the adjacent PQEQLT polar face provides a minimal self-sufficient amphipathic unit.
Why it’s plausible
The full 55-residue sequence exceeds the practical SPPS limit noted in the manufacturing literature (~50 residues), and at 55 aa the peptide is already at the boundary where synthesis cost and aggregation risks rise sharply. The C-terminal region KPQEQLTPVIYPAV contains a positively charged lysine, a polar glutamine-rich stretch, and the strongly hydrophobic PVIYPAV tail, constituting a self-contained amphipathic unit. Proline at the N-terminus of both PQEQLT and PVIYPAV sub-segments introduces rigidity that resists exopeptidase degradation. The manufacturing literature explicitly flags SPPS at >50 residues as prohibitively expensive and prone to aggregation, motivating truncation studies.
Why it matters
Identifying a minimal active fragment would overcome the primary manufacturing barrier for this peptide class and yield a candidate with more predictable pharmacokinetics.
Plausibility.52
Novelty.38
Impact.65
Basis · grounding2 papers · 1 computed/note
[1]
sequenceC-terminal KPQEQLTPVIYPAV (15 residues) contains K (cationic), polar PQEQLT, and hydrophobic PVIYPAV with proline-gated termini; full length 55 aa is above the practical SPPS threshold
[2]
paper
SPPS peptide length should be no more than 50 amino acids; hydrophobic peptides tend to aggregate in solvent during synthesis
doi: 10.1038/nbt1267
[3]
paper
Recombinant production is more useful for large peptides; chemical synthesis cost decreases but remains an issue for long sequences
doi: 10.1002/psc.3137
openupdated 2026-06-05

Could this peptide tell cancerous cells apart from normal ones by sensing a surface molecule that tumours accidentally expose?

Many cancer drugs cause collateral damage to healthy tissue. If this peptide targets a marker that cancer cells display and normal cells do not, it could kill tumours while leaving surrounding tissue largely unharmed, potentially reducing side effects for patients.

The hypothesis
pep-05243 selectively kills cancer cells over normal epithelial cells because its net positive charge directs it toward the phosphatidylserine-rich outer leaflet of malignant membranes, and this selectivity is diminished when extracellular phosphatidylserine is masked or neutralized.
Why it’s plausible
Normal mammalian cell membranes present zwitterionic phosphatidylcholine and sphingomyelin on the outer leaflet, while many cancer types (breast, colon, pancreatic) constitutively expose phosphatidylserine. The K and H residues in HKLQ and KALI patches give pep-05243 a positive charge that electrostatically enriches it at anionic cancer-cell surfaces before hydrophobic insertion. This mechanism is distinct from simple cytotoxicity because charge neutralization or competitive anionic lipid addition should specifically abrogate cancer-cell killing without equivalent effect on normal cells. The food-protein origin refs emphasize that tumor-selectivity without damaging normal cells is a key outstanding question for such peptides.
Why it matters
Confirming phosphatidylserine-dependent selectivity would position pep-05243 within a mechanistic class where tumor selectivity is inherent rather than engineered, shortening the path to therapeutic development.
Plausibility.58
Novelty.20
Impact.70
Basis · grounding2 papers · 1 computed/note
[1]
sequenceK8, H13, K16, K23, K28, K42 provide distributed positive charge compatible with anionic membrane attraction
[2]
paper
Selectivity for tumor cells without damaging normal cells is stated as very important but mechanistically underexplored for food-derived anticancer peptides
doi: 10.1016/j.foodchem.2017.10.087
[3]
paper
Cancer cells co-express multiple peptide receptors and surface markers that differ from normal cells, supporting surface-charge-based targeting strategies
doi: 10.7150/thno.4024
openupdated 2026-06-05

Does a floppy middle section in the peptide act like a hinge, letting each end anchor into a cell's outer wall from opposite sides?

Understanding exactly how the peptide's shape drives its activity would let researchers engineer shorter or more stable versions with better performance, which could speed up the path toward a usable treatment.

The hypothesis
The GGAMMAK central hinge (residues 37-43) acts as a flexible pivot that allows pep-05243 to adopt a boomerang-like conformation in solution, with the N-terminal hydrophobic arm (GCVWPDGK) and C-terminal hydrophobic arm (PVIYPAV) cooperating to span and bridge opposing membrane leaflets, a geometry that would be abolished by rigidifying substitutions at either G37 or G38.
Why it’s plausible
Consecutive glycines provide maximum backbone flexibility. The sequence architecture shows two hydrophobic clusters separated by a polar charged mid-section, with a GG doublet at positions 37-38 providing a natural hinge. Double-glycine hinges appear in membrane-active peptides (such as gramicidin-related fragments) where they allow the peptide to fold back on itself. GGAMMAK also contains two alanines and one methionine that contribute modest helix-forming propensity locally. If the two hydrophobic termini act as independent membrane-inserting anchors connected by a flexible linker, the peptide topology would resemble a U-shaped membrane staple. This is directly testable by proline substitution at G37 or G38 to rigidify the hinge.
Why it matters
Identifying the structural basis of membrane activity would guide rational truncation or cyclization engineering to improve potency or reduce the peptide to a minimal active fragment.
Plausibility.35
Novelty.53
Impact.52
Basis · grounding1 paper · 2 computed/notes
[1]
sequenceGG at positions 37-38 flanked by AMMAK on one side and KSIAT on the other; N-terminal GCVWP and C-terminal PVIYPAV are both hydrophobic clusters separated by 25+ polar residues
[2]
structureBoltz-2 structure prediction computed (boltz-2 on vast_v100_32gb); a low-confidence extended conformation would support flexible hinge hypothesis over a compact globular fold
[3]
paper
Head-to-tail cyclization of short cationic anticancer peptides improved anticancer potency, implying that conformational constraint at the termini modulates activity
doi: 10.1021/acs.jmedchem.5b02025
details expand to inspect
full evidence table1 metrics
metricvaluetool
ranking score 0.44210514426231384 boltz-2
3-letter notation
Gly-Cys-Val-Trp-Pro-Asp-Gly-Lys-Ala-Ile-Thr-Thr-His-Lys-Leu-Gln-Thr-Thr-Met-Leu-Glu-Thr-Lys-Ala-Leu-Ile-Met-Gly-Tyr-Phe-Lys-Ser-Ile-Ala-Thr-Gly-Gly-Ala-Met-Met-Ala-Lys-Pro-Gln-Glu-Gln-Leu-Thr-Pro-Val-Ile-Tyr-Pro-Ala-Val
recipeboltz-2 2.2.1
parametervalue
modelboltz-2 2.2.1
weights
hardwarevast_v100_32gb
mlx version
python
random seed1
msa strategynone_monomer
runtime
predicted by
predicted at2026-05-23
citationbibtex
peptidemodel (2026). Experimental anticancer peptide (pep-05243, v1). PeptideModel. https://peptidemodel.com/card/pep-05243
@peptide{pep05243,
  sequence = {GCVWPDGKAITTHKLQTTMLETKALIMGYFKSIATGGAMMAKPQEQLTPVIYPAV},
  target   = {anticancer},
  author   = {peptidemodel},
  year     = {2026},
  status   = {bioassayed}
}
related peptides 5 by signal overlap
references 3 papers
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