pep-05196 v1 CC-BY-SA-4.0
Temporin-CDYb cancer-fighting peptide
An experimental peptide studied in the lab for its ability to attack cancer cells.
status
Someone proposed this peptide.
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
A computer predicted how the peptide binds to its target.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
Someone else ran the same prediction and got the same result.
A second contributor repeated the computation on their own hardware and the scores matched.
The peptide was actually made in a lab.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
The peptide was tested on its target in a lab.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
prediction metrics
ipTM0.000
pTM0.454
avg pLDDT68.5
ranking score0.639
STRUCTURE · PEP-05196 × ANTICANCER
ranking0.639
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
sequence
151015202530354045505560
MFTLKKSLLLLFFLGTINLS LCEEERNADEERRDDPEERA VEVEKRILPILSLIGGLLGK
in the news
Hypotheses6 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
Is the whole protein doing the work, or just one small piece of it?
If only the 15-amino-acid tail fragment is the real active unit, researchers could synthesize and test just that piece instead of the full 60-unit protein, making drug development faster and cheaper. Getting this wrong early wastes years of experiments on the wrong molecule.
The hypothesis
The biologically active unit of pep-05196 is the C-terminal segment RILPILSLIGGLLGK released after proteolytic processing at the dibasic KR site (positions 44-45), and this 15-residue peptide adopts an amphipathic alpha-helix responsible for membrane disruption in cancer cells.
Why it’s plausible
The 60-aa sequence encodes a canonical ranid AMP precursor architecture: a conserved hydrophobic signal peptide (MFTLKKSLLLLFF), an anionic acidic spacer (EEERNADEERRDDPEER), a dibasic processing site (KR at positions 44-45), and a cationic C-terminal mature peptide (RILPILSLIGGLLGK). Closely related precursors such as odorranain-G-OT and tiannanensin follow exactly this pattern. The mature segment has the hallmark temporin composition: short, amphipathic, positively charged, with a C-terminal lysine anchor. The full precursor plddt of 68.5 is consistent with a largely disordered scaffold, not a folded active form. The C-terminal segment alone would be predicted to fold into an amphipathic helix upon membrane contact.
Why it matters
Misidentifying the full 60-aa precursor as the active peptide would give misleading potency and selectivity data. Confirming that only RILPILSLIGGLLGK is the active unit defines the correct minimal pharmacophore for synthesis, SAR, and engineering efforts.
Plausibility.68
Novelty.43
Impact.85
Basis · grounding1 paper · 2 computed/notes
[1]
Sequence alignment shows odorranain-G-OT has the same MFTLKKSLLLLFF signal and anionic spacer architecture, with a dibasic KR cleavage site preceding the mature peptide
doi: 10.1016/j.biochi.2011.09.017[2]
[3]
openupdated 2026-06-05
Can something kill cancer cells without also destroying healthy blood cells?
Many cancer-killing peptides fail because they also burst red blood cells, making them too toxic to use. If this peptide's structure gives it a favorable safety profile, it could potentially advance toward animal studies without hitting that common wall.
The hypothesis
The mature temporin-CDYb peptide is selectively cytotoxic against cancer cells with high phosphatidylserine exposure but shows low hemolytic activity because its hydrophobicity is insufficient to disrupt cholesterol-rich erythrocyte membranes at the same concentrations.
Why it’s plausible
Within the temporin family, the therapeutic index (cancer cell IC50 versus erythrocyte HC50) tracks closely with the hydrophobic moment and net charge balance. The mature segment RILPILSLIGGLLGK has two charged residues (R, K) and a run of hydrophobic residues, but the GGLLG motif introduces helix-breaking glycines that may reduce the hydrophobic face area, limiting membrane disruption of cholesterol-stiffened erythrocytes while still permitting disruption of the more fluid, PS-rich cancer cell membrane. Temporin-PE analog studies in the axis hits show that small changes in hydrophobicity segregate anticancer from hemolytic activity, with some analogs achieving a favorable index.
Why it matters
If the glycine-interrupted hydrophobic face of RILPILSLIGGLLGK gives a favorable therapeutic index, this peptide or its analogs could advance toward in vivo models without dose-limiting hemolysis, a common failure mode for cationic amphipathic peptides.
Plausibility.53
Novelty.47
Impact.75
Basis · grounding2 papers · 1 computed/note
[1]
Temporin-PE analogs: temporin-PEa lacked serious cytotoxicity on normal HMEC-1 endothelial cells at 10 uM, demonstrating that minor sequence changes determine selectivity between cancer and normal cells
doi: 10.1016/j.bbrc.2017.11.173[2]
Increasing cationicity while maintaining moderate hydrophobicity in temporin-1CEa analogs generated improved cancer selectivity with reduced hemolysis
doi: 10.1007/s12272-013-0112-8[3]
openupdated 2026-06-05
Could one molecule be useful against both cancer and untreatable bacterial infections?
MRSA kills tens of thousands of people yearly and outruns most antibiotics. If this peptide works against MRSA at doses below what it takes to kill cancer cells, it could be worth developing for two serious problems at once, which would strengthen the case for investment.
The hypothesis
The mature temporin-CDYb peptide RILPILSLIGGLLGK has antibacterial activity against Gram-positive pathogens including Staphylococcus aureus and MRSA at concentrations below its cancer cell IC50, making it a dual-use anticancer/anti-MRSA agent.
Why it’s plausible
Temporins are historically defined as the shortest known naturally occurring antimicrobial peptides from frog skin. Every experimentally validated temporin to date (temporin-1CEa, temporin-PE, temporin-SHf, temporin-LT1) displays antibacterial activity, particularly against Gram-positive bacteria, alongside any anticancer activity. The mature segment RILPILSLIGGLLGK shares the cationic amphipathic structural determinants that confer membrane disruption of bacterial membranes (negatively charged phospholipids, no cholesterol). The axis hits include temporin-PE showing killing kinetics against S. aureus and MRSA at 1-8 uM. Given that cancer cell killing and bacterial membrane disruption rely on the same electrostatic and hydrophobic mechanism, the peptide likely retains antibacterial potency at relevant concentrations.
Why it matters
If RILPILSLIGGLLGK is active against MRSA, it addresses an urgent clinical need where resistance to conventional antibiotics is a crisis. A single peptide with dual anticancer and anti-MRSA activity broadens its therapeutic utility and justifies a more comprehensive development program.
Plausibility.65
Novelty.33
Impact.66
Basis · grounding2 papers · 1 computed/note
[1]
Temporin-PE and analogs kill S. aureus and MRSA at 1-8 uM and simultaneously exert anticancer activity against NCI-H157, U251MG, PC-3, and MDA-MB-435s cell lines
doi: 10.1016/j.bbrc.2017.11.173[2]
AMPs from Amolops mantzorum (a ranid frog) disrupt E. coli membranes at 5x MIC, demonstrating that ranid AMPs with similar structural features kill bacteria by direct membrane disruption
doi: 10.2108/zsj.31.143[3]
openupdated 2026-06-05
How does the frog produce a toxic peptide without poisoning itself?
Understanding the natural on/off mechanism could help scientists manufacture this peptide safely in the lab without it killing the production cells. It might also point toward ways to control when and where the peptide activates in a therapeutic context.
The hypothesis
The anionic propeptide region EEERNADEERRDDPEER of the pep-05196 precursor acts as an intramolecular inhibitor that keeps the cationic mature peptide inactive within the producer cell by electrostatic autoinhibition, and this anionic segment could competitively bind the same cationic membrane-active region of the mature peptide when administered exogenously.
Why it’s plausible
In several ranid AMP precursors, the acidic spacer between the signal peptide and the mature peptide is thought to prevent premature membrane lysis in the producing granular gland cells. The EEERNADEERRDDPEER segment in pep-05196 carries approximately eight net negative charges, which would electrostatically neutralize the +2 net charge of the mature RILPILSLIGGLLGK segment. This architecture is conserved in esculentin-2 and odorranain precursors from the reference literature. An exogenously added synthetic anionic propeptide analog could therefore suppress the anticancer or antimicrobial activity of the mature peptide, providing mechanistic evidence for the autoinhibition model and revealing whether the mature peptide is the sole active moiety.
Why it matters
Understanding the propeptide as an intramolecular chaperone and autoinhibitor clarifies the native activation mechanism (likely extracellular protease-dependent), informs recombinant production strategies that avoid premature cell toxicity, and suggests whether propeptide-based analogs could function as modulators.
Plausibility.60
Novelty.48
Impact.53
Basis · grounding2 papers · 1 computed/note
[1]
Esculentin-2 precursors from Chinese ranid frogs share the same three-domain architecture (signal peptide, anionic spacer EOERAADEEDNGEVEEV, dibasic KR, mature cationic peptide), supporting a conserved autoinhibitory propeptide function
doi: 10.1016/j.ygeno.2005.12.002[2]
Odorranain-G-OT precursor sequence alignment shows the anionic NAEEKR domain directly preceding the mature peptide in the same position as in pep-05196
doi: 10.1016/j.biochi.2011.09.017[3]
openupdated 2026-06-05
Does this thing work like a key fitting a lock, or more like a wrecking ball?
If the mechanism is physical membrane rupture rather than binding a specific receptor, cancer cells would have a much harder time evolving resistance to it. That matters because resistance is why most cancer drugs eventually stop working.
The hypothesis
The mature temporin-CDYb peptide (RILPILSLIGGLLGK) kills cancer cells primarily through direct membrane disruption of the negatively charged outer leaflet of tumor plasma membranes, rather than through receptor-mediated intracellular signaling.
Why it’s plausible
Temporin-family peptides derived from ranid frogs are membrane-active: they exploit the elevated phosphatidylserine (PS) exposure on the outer leaflet of cancer cells, a feature absent in healthy mammalian cells where PS is confined to the inner leaflet. The mature segment RILPILSLIGGLLGK carries a net positive charge (R at position 1, K at position 15) and a run of hydrophobic residues (ILP, ILS, GGLLG) that would embed in a bilayer. Temporin-1CEa analogs studied in the axis hits kill MCF-7, MDA-MB-231, and Bcap-37 breast cancer lines via membrane disruption, and structurally similar temporin-PE exerts rapid time-kill kinetics inconsistent with receptor-mediated pathways. The GGLLG motif in particular resembles the glycine hinge found in pore-forming peptides.
Why it matters
Distinguishing membrane lysis from receptor signaling determines whether cancer cells can develop resistance (receptor downregulation is possible; PS externalization is a fundamental feature of cancer cells less amenable to resistance). It also sets the therapeutic window expectations relative to normal cells.
Plausibility.72
Novelty.25
Impact.63
Basis · grounding2 papers · 1 computed/note
[1]
Temporin-1CEa analogs exert anticancer activity against MCF-7, MDA-MB-231 and Bcap-37 via amphipathic alpha-helical membrane disruption; cationicity and moderate hydrophobicity are the key tunable parameters
doi: 10.1007/s12272-013-0112-8[2]
Anticancer peptide mechanisms review confirms membrane disruption as a dominant mode for cationic amphipathic peptides from frog skin
doi: 10.1016/j.cbi.2022.110194[3]
openupdated 2026-06-05
Should scientists try to make this peptide stronger, or would that backfire?
Counter-intuitively, the structural features that limit this peptide's potency against tumors may be the same ones that protect red blood cells from damage. If true, researchers should work around those features rather than remove them, which could save significant time and cost in analog development.
The hypothesis
Substituting one or both glycines in the GGLLG motif of the mature temporin-CDYb peptide with alanine (giving RALLG or AALLG) will increase the amphipathic helical content and the cancer cell cytotoxicity but will disproportionately increase hemolytic activity, meaning the native glycine residues represent a selectivity-preserving constraint that should not be optimized away.
Why it’s plausible
Glycine is a helix breaker; its presence at two adjacent positions in the hydrophobic face of RILPILSLIGGLLGK likely introduces a kink that reduces the effective hydrophobic moment. For temporin-1CEa analogs, increased hydrophobicity enhanced cytotoxicity but also raised hemolysis proportionally, and the optimal therapeutic index was achieved at moderate hydrophobicity. Replacing G-G with A-A in the GGLLG region would extend the hydrophobic face, increasing both potency and hemolytic potential. Replacing only one glycine (G-A) might narrow the hemolytic increase while still boosting potency. This makes the native GGLLG motif a selectivity determinant that should be intentionally preserved in engineering campaigns targeting cancer specificity.
Why it matters
Defining which positions in the mature peptide govern the cancer-versus-erythrocyte selectivity index guides SAR in a productive direction, avoiding the common pitfall of maximizing potency at the cost of therapeutic window. It also identifies the GGLLG glycine hinge as a structural selectivity determinant applicable to other temporin engineering efforts.
Plausibility.46
Novelty.52
Impact.63
Basis · grounding2 papers · 1 computed/note
[1]
Systematic analogs of temporin-1CEa showed that increasing hydrophobicity beyond a moderate threshold raised hemolysis faster than it raised cancer cell cytotoxicity, with the optimal index at moderate hydrophobicity
doi: 10.1007/s12272-013-0112-8[2]
[3]
Disulfide cyclization of temporin-SHf improved trypsin stability without affecting the hydrophobic face, demonstrating that constrained analogs preserve selectivity when the hydrophobic geometry is maintained
doi: 10.1111/cbdd.13525 details
▸full evidence table1 metrics
| metric | value | tool |
|---|---|---|
| ranking score | 0.6392145752906799 | boltz-2 |
▸3-letter notation
Met-Phe-Thr-Leu-Lys-Lys-Ser-Leu-Leu-Leu-Leu-Phe-Phe-Leu-Gly-Thr-Ile-Asn-Leu-Ser-Leu-Cys-Glu-Glu-Glu-Arg-Asn-Ala-Asp-Glu-Glu-Arg-Arg-Asp-Asp-Pro-Glu-Glu-Arg-Ala-Val-Glu-Val-Glu-Lys-Arg-Ile-Leu-Pro-Ile-Leu-Ser-Leu-Ile-Gly-Gly-Leu-Leu-Gly-Lys
▸recipeboltz-2 2.2.1
| parameter | value |
|---|---|
| model | boltz-2 2.2.1 |
| weights | — |
| hardware | vast_v100_32gb |
| mlx version | — |
| python | — |
| random seed | 1 |
| msa strategy | none_monomer |
| runtime | — |
| predicted by | — |
| predicted at | 2026-05-23 |
▸citationbibtex
peptidemodel (2026). Temporin-CDYb cancer-fighting peptide (pep-05196, v1). PeptideModel. https://peptidemodel.com/card/pep-05196
@peptide{pep05196,
sequence = {MFTLKKSLLLLFFLGTINLSLCEEERNADEERRDDPEERAVEVEKRILPILSLIGGLLGK},
target = {anticancer},
author = {peptidemodel},
year = {2026},
status = {computed}
} related peptides
references
[4] supporting
discussion
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