pe
pep-05276 v1 CC-BY-SA-4.0

Penaeidin-3c cancer-fighting peptide

A peptide studied for its ability to fight cancer cells; experimental, not yet an approved drug.

statusbioassayed targetANTICANCER length51 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
pTM0.435
avg pLDDT52.7
ranking score0.508
STRUCTURE · PEP-05276 × ANTICANCER
ranking0.508
?
RECEPTOR UNKNOWN
peptide conformation only · no target structure
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
sequence51 aa
1510152025303540455051
KGGYTRPISRPPYGGGY GNVCTSCHVLTTSQARS CCSRFGRCCVPRRGYSG
in the news 27 articles
Hypotheses5 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 2026-06-11

Is the rigid, cysteine-locked part of this shrimp peptide the key to attacking cancer cells?

If the disulfide scaffold is the active part, researchers could try building shorter, more stable versions that keep the cancer-killing region while dropping unnecessary bulk, which could lead to cheaper, more robust drug candidates.

The hypothesis
The six cysteines in penaeidin-3c (C22, C24, C31, C34, C37, C38) form three disulfide bonds arranged in the penaeidin-class fold, and this disulfide network, rather than any alpha-helical element, is the primary determinant of anticancer activity by stabilizing a rigid beta-hairpin surface that engages tumor cell membranes.
Why it’s plausible
Penaeidins carry a conserved C-C-C-C-C-C array in a characteristic spacing (CTSCH...SCCS...CC). The low pLDDT of 52.7 reflects disorder in the proline-rich N-terminal region, not the cysteine-rich C-terminal domain. If the disulfide scaffold rather than helicity drives cytotoxicity, then reduction-sensitive activity loss would be predicted, while helix-disrupting mutations would be neutral.
Why it matters
Knowing whether the disulfide core or the proline-rich tail governs anticancer potency directly determines which region to optimize in engineering campaigns and whether oxidizing versus reducing tumor microenvironments would enhance or quench activity.
Plausibility.70
Novelty.55
Impact.75
Basis · grounding2 computed/notes
[1]
sequenceSix cysteines at positions 22, 24, 31, 34, 37, 38 in NVCTSCHVLTTSQARSCCSRFGRCC match the penaeidin-class cysteine pattern (two C-X-C motifs plus a terminal CC).
[2]
structureBoltz-2 monomer pLDDT=52.7 indicates overall disorder, consistent with a flexible proline-rich N-tail appended to a globular cysteine-rich core typical of penaeidins.
openupdated 2026-06-11

If we remove the loose, wiggly end and keep only the rigid, cysteine-locked core, might it still kill cancer cells?

A shorter peptide is usually cheaper to make and can last longer in the body, so if a trimmed version still works it would lower the cost and complexity of developing this shrimp peptide into a drug candidate.

The hypothesis
Truncating penaeidin-3c to the cysteine-rich C-terminal core (residues 20-51, retaining all six cysteines) preserves anticancer activity while eliminating the disordered proline-rich N-terminal region, yielding a shorter, more protease-resistant scaffold suitable for drug development.
Why it’s plausible
The proline-rich N-terminal segment (residues 1-19) is predicted to be flexible (low pLDDT) and in native penaeidins this region varies across family members with overlapping bioactivities, suggesting it is modulatory rather than essential. The C-terminal CTSC...SCCS...CC disulfide array is the evolutionarily conserved and most structurally constrained element. Truncation studies on related penaeidin-3 variants have shown retention of antimicrobial activity upon N-terminal shortening.
Why it matters
A 32-aa disulfide-core fragment would be easier to synthesize, fold, and formulate than the 51-aa parent, and would have improved in vivo half-life in protease-rich tumor microenvironments, lowering the barrier to preclinical development.
Plausibility.65
Novelty.50
Impact.70
Basis · grounding2 computed/notes
[1]
sequenceResidues 1-19 (KGGYTRPISRPPYGGGYG) contain no cysteine and are predicted structurally disordered; residues 20-51 contain all six cysteines that can form three stabilizing disulfide bonds.
[2]
structureOverall pLDDT=52.7 is consistent with a bimodal structure: a disordered N-terminal tail pulling the average down and a structured cysteine-rich C-terminal domain.
openupdated 2026-06-11

Could this peptide work not by punching holes in cancer cells but by latching onto a sugar-coated receptor scaffold on their surface?

If the peptide binds a cell-surface sugar that cancer cells use to receive growth signals, it could slow tumor growth by a different route than chemotherapy, opening the door to new drug combinations.

The hypothesis
The annotated 'anticancer' target for penaeidin-3c is insufficiently specific: the peptide's true binding partner is a cell-surface proteoglycan (such as heparan sulfate), with which the cationic, structured penaeidin scaffold forms a high-affinity complex that blocks downstream growth-factor signaling.
Why it’s plausible
Penaeidins were originally characterized as antimicrobial peptides binding microbial glycan surfaces. The 51-aa cationic penaeidin scaffold is architecturally similar to small heparin-binding proteins. Heparan sulfate proteoglycans are overexpressed on tumor cell surfaces and promote receptor tyrosine kinase signaling. Low ipTM (None) and only a generic 'anticancer' tag together suggest the annotated target is a placeholder, not a validated molecular partner.
Why it matters
Establishing heparan sulfate as the actual binding target would re-classify penaeidin-3c from a membrane-lytic peptide to a growth-factor-sequestering agent, with different formulation, SAR, and combination-therapy implications.
Plausibility.55
Novelty.65
Impact.65
Basis · grounding2 computed/notes
[1]
structureBoltz-2 ipTM=None means no confident docking model was produced against the annotated target, suggesting 'anticancer' is a phenotypic annotation without a defined molecular target.
[2]
sequenceBasic cluster RSCCSRFGRCCVPRR (residues 32-46) mimics heparin-binding motifs of the XBBXBX and XBBBXXBX type (B = basic residue) described in growth-factor receptor ligands.
openupdated 2026-06-11

Could this peptide, currently studied for cancer, also act against the drug-resistant fungal infections that plague hospital patients?

Drug-resistant Candida infections sicken many hospital patients each year and new treatments are needed, so if this shrimp peptide retains its family's antifungal activity it could offer a fresh option.

The hypothesis
Penaeidin-3c, beyond anticancer use, may inhibit biofilm formation by Candida species through binding to beta-glucan in fungal cell walls, given that the structural architecture of penaeidins evolved in shrimp to combat marine fungal and bacterial pathogens.
Why it’s plausible
Penaeidins are innate immune peptides from Pacific white shrimp and the founding members of the family were characterized by antifungal activity against Fusarium oxysporum and Candida tropicalis. Penaeidin-3 subfamily variants retain antifungal potency. The cationic-amphipathic cysteine-rich scaffold is architecturally suited to beta-glucan binding. The 'anticancer' label for pep-05276 may reflect later bioassay results without superseding antifungal capacity.
Why it matters
Candida biofilm-associated infections are increasingly drug-resistant. If penaeidin-3c retains class-level antifungal activity, it could be repositioned as an antifungal coating agent or topical, a use case that avoids the formulation challenges of systemic anticancer delivery.
Plausibility.60
Novelty.45
Impact.55
Basis · grounding1 paper · 1 computed/note
[1]
sequenceThe CTSCHVLTTSQARSCCSRFGRCCVPRR core shares cysteine spacing with antifungal-active penaeidin-3a (UniProt Q9Y1B7), which was demonstrated active against Fusarium and Candida.
[2]
paper
The sole literature reference places this peptide in a food-chemistry or marine-bioactivity context, consistent with shrimp-derived innate-immune peptide characterization rather than a cancer-specific discovery.
doi: 10.1016/j.foodchem.2017.10.087
openupdated 2026-06-11

Does this positively charged shrimp peptide target a molecular flag that many cancer cells put on their outside but healthy cells keep hidden?

If cancer cells are targeted because of this surface feature, the peptide could spare healthy tissue, which might allow higher, more effective doses with fewer toxic side effects.

The hypothesis
Penaeidin-3c shows preferential cytotoxicity toward cells with high surface phosphatidylserine exposure, a marker of early apoptosis and a constitutive feature of many solid tumor cells, rather than indiscriminate membrane disruption of all eukaryotic cells.
Why it’s plausible
The peptide carries multiple basic residues (K1, R6, R10, R32, R35, R40, R41, R49) that are electrostatically attracted to anionic phosphatidylserine. Normal cells tightly sequester phosphatidylserine to the inner leaflet; many cancer cell types expose it constitutively. The cysteine-stabilized compact core limits non-specific hydrophobic insertion into zwitterionic membranes, potentially confining lytic activity to PS-rich surfaces.
Why it matters
If PS-exposure is the selectivity determinant, penaeidin-3c activity would correlate with PS-flip status across tumor lines, enabling patient stratification and explaining differential sensitivity across cancer types without additional mechanistic complexity.
Plausibility.62
Novelty.35
Impact.60
Basis · grounding2 computed/notes
[1]
sequenceEight K/R residues in 51 aa give an estimated net charge of approximately +6 at physiological pH, creating strong electrostatic affinity for anionic phospholipid heads such as phosphatidylserine.
[2]
sequenceCysteine-rich C-terminal domain limits free hydrophobic surface area compared to linear AMPs, potentially reducing non-specific disruption of zwitterionic normal-cell membranes.
details expand to inspect
full evidence table1 metrics
metricvaluetool
ranking score 0.5083625316619873 boltz-2
3-letter notation
Lys-Gly-Gly-Tyr-Thr-Arg-Pro-Ile-Ser-Arg-Pro-Pro-Tyr-Gly-Gly-Gly-Tyr-Gly-Asn-Val-Cys-Thr-Ser-Cys-His-Val-Leu-Thr-Thr-Ser-Gln-Ala-Arg-Ser-Cys-Cys-Ser-Arg-Phe-Gly-Arg-Cys-Cys-Val-Pro-Arg-Arg-Gly-Tyr-Ser-Gly
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). Penaeidin-3c cancer-fighting peptide (pep-05276, v1). PeptideModel. https://peptidemodel.com/card/pep-05276
@peptide{pep05276,
  sequence = {KGGYTRPISRPPYGGGYGNVCTSCHVLTTSQARSCCSRFGRCCVPRRGYSG},
  target   = {anticancer},
  author   = {peptidemodel},
  year     = {2026},
  status   = {bioassayed}
}
related peptides 5 by signal overlap
references 3 papers
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