pe
pep-05263 v1 CC-BY-SA-4.0

SPAG11B experimental anticancer peptide

A lab-made peptide being studied for its potential to fight cancer cells; experimental, not an approved drug.

statusbioassayed targetANTICANCER length53 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
pTM0.443
avg pLDDT55.6
ranking score0.534
STRUCTURE · PEP-05263 × ANTICANCER
ranking0.534
?
RECEPTOR UNKNOWN
peptide conformation only · no target structure
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
sequence53 aa
1510152025303540455053
DLLPPRTPPYQEPASDLK VVDFRRSEGFCQEYCNYM ETQVGYCPKKKDACCLH
in the news 27 articles
Hypotheses3 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 the same molecule that attacks tumor cells also kill harmful bacteria, at doses lower than the ones used against cancer?

If this holds, a single peptide could help oncology patients on two fronts: fighting their cancer and protecting them from bacterial infections at the same time. That would be especially valuable for cancers already linked to bacteria, like certain stomach cancers tied to H. pylori.

The hypothesis
pep-05263 possesses direct antimicrobial activity against gram-negative bacteria at concentrations below its cancer cell cytotoxic IC50, because its beta-defensin scaffold and cationic cluster are structurally analogous to antimicrobial defensins active against bacterial outer membranes.
Why it’s plausible
SPAG11B is classified as a beta-defensin and the full-length protein has documented broad-spectrum antimicrobial activity. The 53-residue peptide retains the cysteine framework and the PKKKD polycationic motif that in related defensins mediates insertion into negatively charged bacterial outer membranes. Proline-rich stretches (LLPP, RTPP) are also a hallmark of proline-rich antimicrobial peptides active against gram-negative bacteria. The literature references are exclusively about anticancer activity, leaving antimicrobial potential unexplored for this specific sequence.
Why it matters
If the peptide has dual anticancer and antibacterial activity at non-overlapping dose ranges, it could be relevant for treating cancers associated with bacterial co-infections (e.g., H. pylori in gastric cancer) or for preventing infection in immunocompromised oncology patients.
Plausibility.47
Novelty.55
Impact.53
Basis · grounding2 papers · 1 computed/note
[1]
sequenceProline doublets LLPP and RTPP at N-terminus; PKKKD cationic cluster; defensin-type cysteine spacing collectively matching antimicrobial peptide structural signatures
[2]
paper
Parent SPAG11B from egg white has documented antimicrobial properties; egg-derived defensins are reviewed in this anticancer peptide review context
doi: 10.3382/ps/pez381
[3]
paper
Anticancer peptides mechanisms review notes many ACPs share structural features with antimicrobial peptides and may have dual activity
doi: 10.1016/j.cbi.2022.110194
openupdated 2026-06-05

If the two ends of this molecule each do their own job independently, could we keep just one end and still keep the benefits?

Long peptides are expensive and difficult to manufacture. If the cancer-killing activity lives mostly in one end of this molecule, chemists could potentially build a shorter version that is cheaper to produce and still just as effective, making it more practical to develop as a therapy.

The hypothesis
The two proline-rich N-terminal segments (LLPP and RTPP) impose a rigid, extended conformation on the first 10 residues of pep-05263, preventing alpha-helical folding and functionally uncoupling the N-terminal domain from the C-terminal disulfide-constrained beta-defensin core, such that the two halves exert independent and additive cytotoxic contributions.
Why it’s plausible
Proline is helix-breaking; tandem XP motifs impose backbone rigidity. In the 53-residue sequence, positions 3-4 (LLPP) and 7-8 (RTPP) create a proline-rich linker that would resist alpha-helix formation in that segment. The C-terminal half contains the cysteine-rich defensin core responsible for membrane interaction. If the N-terminal domain folds independently (possibly as a polyproline type II helix), it may engage a different surface feature (e.g., a receptor or co-receptor) while the C-terminal core handles membrane insertion. Truncation studies on analogous bifunctional defensins have shown loss of different activities when N-terminal or C-terminal halves are removed separately.
Why it matters
Demonstrating functional independence of the two structural domains would justify designing minimized analogues retaining only the C-terminal defensin core for simpler synthesis (the full 53-residue length already approaches the practical SPPS limit) without sacrificing potency.
Plausibility.49
Novelty.45
Impact.55
Basis · grounding2 papers · 1 computed/note
[1]
sequenceResidues 3-4: LL-PP and 7-8: RT-PP create two consecutive XPP motifs that are incompatible with alpha-helix formation; C-terminal segment from residue 30 onward contains all five cysteines
[2]
paper
Manufacturing note that SPPS is limited to ~50 amino acids, making this 53-residue peptide at the cost-prohibitive boundary; domain-truncated analogues would address this
doi: 10.1038/s41467-023-37003-z
[3]
paper
Natural ACPs with sequences over 30 amino acids incur high synthesis costs; the N-terminal segment here is a candidate for truncation if functionally separable
doi: 10.1016/j.omto.2019.12.001
openupdated 2026-06-05

Does this molecule destroy cancer cells by physically disrupting their outer membrane, the way soap dissolves grease?

If the killing comes from physically disrupting the membrane rather than binding one specific protein, then what matters most is how well it tells cancer cells apart from healthy ones. It would also change how researchers improve it: the focus would shift to fine-tuning its electrical charge and shape rather than hunting for a molecular target.

The hypothesis
The cationic lysine cluster (PKKKD) in the C-terminal region of pep-05263 drives electrostatic disruption of negatively charged cancer cell membranes as its primary cytotoxic mechanism, rather than engagement of a specific intracellular target.
Why it’s plausible
The sequence contains a contiguous KKK triplet flanked by proline and aspartate at positions ~44-48. Beta-defensins with analogous cationic clusters are established membrane-active agents that exploit the elevated phosphatidylserine exposure on cancer cell outer leaflets. The absence of any annotated molecular target and the derivation from SPAG11B, a cationic defensin, both support a membrane-disruption rather than receptor-mediated mechanism. The proline-rich N-terminal segment (LLPP, RTPP) could limit helical folding and bias the peptide toward a membrane-thinning toroidal or carpet mode.
Why it matters
If the mechanism is membrane disruption rather than receptor binding, the therapeutic window depends primarily on selectivity for cancer vs. normal cell membrane composition, and engineering efforts should focus on tuning charge density and amphipathicity rather than on target affinity optimization.
Plausibility.34
Novelty.22
Impact.68
Basis · grounding1 paper · 2 computed/notes
[1]
sequenceKKK triplet at positions ~44-46 and multiple cysteines (C32, C36, C45, C50, C51) defining a cationic, disulfide-constrained scaffold
[2]
sourceSPAG11B parent protein is a beta-defensin with documented membrane-active antimicrobial and anticancer properties from egg whites
[3]
paper
Hydrophobicity and cationic charge are noted as critical determinants of membrane-targeting anticancer peptide mechanism
doi: 10.1158/1535-7163.mct-10-0811
details expand to inspect
full evidence table1 metrics
metricvaluetool
ranking score 0.5337924361228943 boltz-2
3-letter notation
Asp-Leu-Leu-Pro-Pro-Arg-Thr-Pro-Pro-Tyr-Gln-Glu-Pro-Ala-Ser-Asp-Leu-Lys-Val-Val-Asp-Phe-Arg-Arg-Ser-Glu-Gly-Phe-Cys-Gln-Glu-Tyr-Cys-Asn-Tyr-Met-Glu-Thr-Gln-Val-Gly-Tyr-Cys-Pro-Lys-Lys-Lys-Asp-Ala-Cys-Cys-Leu-His
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). SPAG11B experimental anticancer peptide (pep-05263, v1). PeptideModel. https://peptidemodel.com/card/pep-05263
@peptide{pep05263,
  sequence = {DLLPPRTPPYQEPASDLKVVDFRRSEGFCQEYCNYMETQVGYCPKKKDACCLH},
  target   = {anticancer},
  author   = {peptidemodel},
  year     = {2026},
  status   = {bioassayed}
}
related peptides 5 by signal overlap
references 3 papers
discussion no comments
sign in to comment
peptidemodel.com CC-BY-SA-4.0 research only · not for human use