pe
pep-05503 v1 CC-BY-SA-4.0

Temporin-CDYe antimicrobial peptide

A naturally occurring peptide that kills or disables harmful bacteria and microbes; used only as a lab research tool.

statuscomputed targetANTIMICROBIAL length59 aa refs1
antimicrobial
EARLY ENTRY This candidate is newly indexed — supporting evidence is still being added. Have a paper or data point? Contribute below.
status 2 / 5 · 2 contributors
prediction metrics boltz-2 2.2.1
ipTM0.000
pTM0.438
avg pLDDT66.3
ranking score0.618
STRUCTURE · PEP-05503 × ANTIMICROBIAL
ranking0.618
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RECEPTOR UNKNOWN
peptide conformation only · no target structure
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
sequence59 aa
151015202530354045505559
MFTLKKSMLLLLFLGTISLT LCEEERDANEEEENGGEVKV EEKRFIGPIISALASLFGG
in the news 6 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 2026-06-05

Does the full protein need to be cut down before it can fight bacteria, and if so, exactly where?

Many natural peptide antibiotics are first made as a longer, inactive form and only become active after being trimmed. If researchers can confirm precisely which piece of this frog-skin molecule is the live antibiotic, every future experiment, drug design effort, and safety test would be working with the right molecule, not a guess.

The hypothesis
The mature bioactive peptide of Temporin-CDYe is restricted to the C-terminal amphipathic segment EVKVEEKRFIGPIISALASLFGG, and the full 59-residue precursor sequence (including signal peptide and acidic pro-region) is biologically inactive until proteolytically processed at the skin secretory granule stage.
Why it’s plausible
The full sequence MFTLKKSMLLLLFLGTISLTLCEEERDANEEEENGGEVKVEEKRFIGPIISALASLFGG clearly encodes a tripartite precursor: a hydrophobic signal peptide (MFTLKKSMLLLLFLGTISLTLC), an acidic spacer rich in glutamate (EEERDANEEEENGG), and a C-terminal region (EVKVEEKRFIGPIISALASLFGG) containing the cationic and hydrophobic residues characteristic of antimicrobial temporins. The reference (10.1016/j.cbpb.2009.05.015) isolates this peptide via RT-PCR from precursor mRNA, not from purified skin secretion, so the actual mature peptide boundaries have not been experimentally confirmed. The acidic pro-region is known across many frog AMP families to neutralize and sequester the cationic mature peptide in the granule.
Why it matters
Misidentifying the active form confounds all downstream potency, selectivity, and structure-activity work. Confirming the mature peptide boundaries is prerequisite to rational engineering of Temporin-CDYe.
Plausibility.57
Novelty.37
Impact.85
Basis · grounding1 paper · 1 computed/note
[1]
sequenceN-terminal MFTLKKSMLLLLFLGTISLTLC fits hydrophobic signal peptide; EEERDANEEEENGG is a glutamate-rich acidic pro-region; EVKVEEKRFIGPIISALASLFGG is the cationic/hydrophobic C-terminal mature-peptide candidate.
[2]
paper
Peptide was characterized from RT-PCR of skin RNA, not from purified secretion, meaning only the precursor ORF was determined.
doi: 10.1016/j.cbpb.2009.05.015
openupdated 2026-06-05

Can scientists adjust one tiny part of this peptide so it still kills Staph bacteria but is safer for human cells?

A major roadblock for turning natural peptide antibiotics into usable drugs is that they can also destroy red blood cells. If this targeted substitution works, it could open a path toward a safer antibiotic candidate for treating skin or wound infections caused by Staphylococcus aureus.

The hypothesis
Substituting the FIGP tetrapeptide at the N-terminal end of the hydrophobic core with FLGP or FLSP will selectively reduce hemolytic activity of Temporin-CDYe without abolishing antimicrobial potency against Staphylococcus aureus.
Why it’s plausible
The temporin-PE study (10.1016/j.bbrc.2017.11.173) showed that modifying the FLP motif reduced hemolysis while retaining antibacterial effect. Temporin-CDYe contains FIGP at the analogous position; isoleucine at position 2 of this motif is a large branched hydrophobic residue that may increase bilayer insertion depth into cholesterol-rich mammalian membranes. Replacing I with L (smaller side-chain volume) or S (hydrophilicity break) is predicted to reduce insertion into mammalian membranes while the overall helical scaffold and net charge remain sufficient for bacterial targeting. This is a specific, testable structural claim about a named substitution.
Why it matters
A non-hemolytic analog of Temporin-CDYe with retained potency would address a key safety barrier for topical or systemic antibiotic development from this natural scaffold.
Plausibility.40
Novelty.37
Impact.60
Basis · grounding2 papers · 1 computed/note
[1]
sequenceMature candidate contains FIGP at the hydrophobic core entry point; I191 is analogous to the L in FLP motifs of other temporins.
[2]
paper
FLP motif modifications in temporin-PE decreased hemolysis and also reduced anti-proliferative activity while retaining antibacterial MIC values.
doi: 10.1016/j.bbrc.2017.11.173
[3]
paper
SAR study of temporin-SHf shows added charge and hydrophilic substitutions tune antibacterial efficiency and toxicity independently.
doi: 10.1021/acschembio.5b00495
openupdated 2026-06-05

Is this antibiotic peptide too indiscriminate, attacking human blood cells as well as bacteria?

If the suspicion holds, this peptide in its current form would have a narrow safety margin and could not be used as-is in patients. Confirming the problem would also point directly to which part of the molecule needs to be redesigned, giving researchers a clear starting point for safer analogs.

The hypothesis
Temporin-CDYe has poor selectivity for bacterial over mammalian membranes because the highly hydrophobic FIGPIISALASLFGG segment confers hemolytic activity, analogous to the FLP-motif-driven hemolysis documented for temporin-PE.
Why it’s plausible
The axis hit from 10.1016/j.bbrc.2017.11.173 explicitly identifies an FLP-containing hydrophobic motif in temporin-PE as the structural determinant of hemolysis: 'the FLP motif, as previously shown for other similar peptides, is associated with the hemolytic activity of temporin-PE.' The mature candidate of CDYe contains FIGP at equivalent position. The 15-residue run FIGPIISALASLFGG is among the most hydrophobic segments seen in temporins, and excessive hydrophobicity correlates with non-selective membrane lysis. Without counterbalancing cationic charge sufficient to enforce selectivity, this peptide may lyse red blood cells at concentrations near the MIC.
Why it matters
If confirmed hemolytic, the therapeutic window of CDYe is narrow and rational analog design must substitute or truncate the FIGP anchor to dissociate antimicrobial potency from toxicity, as done for temporin-PE analogs.
Plausibility.42
Novelty.33
Impact.57
Basis · grounding1 paper · 1 computed/note
[1]
sequenceCandidate mature peptide begins EVKVEEKRFIGPIISALASLFGG; FIGP motif at position 9 of mature region mirrors the hemolytic FLP motif of temporin-PE.
[2]
paper
FLP motif in temporin-PE drives hemolysis; modifying this motif reduced hemolytic activity while retaining antimicrobial potency.
doi: 10.1016/j.bbrc.2017.11.173
openupdated 2026-06-05

Could this natural antibiotic miss a whole class of harmful bacteria because it cannot get through their outer shell?

Knowing which bacteria a peptide can and cannot reach narrows down the infections it might realistically treat, such as Staph skin infections versus gut or bloodstream infections caused by tougher Gram-negative bugs. If the limitation is confirmed, researchers could potentially pair it with a companion molecule to broaden its reach.

The hypothesis
Temporin-CDYe has negligible antimicrobial activity against Gram-negative bacteria because the short cationic segment EVKVEEKR in the mature peptide is insufficient to traverse the outer membrane lipopolysaccharide barrier without synergistic partner peptides.
Why it’s plausible
Temporins are well-documented to be predominantly active against Gram-positive organisms. The outer membrane of Gram-negative bacteria presents a dense LPS barrier that requires either sustained cationic charge or outer-membrane permeabilizers to cross. The candidate mature peptide of CDYe has only eight residues before the hydrophobic core, and the net charge may not be high enough for autonomous Gram-negative penetration. Synergy between temporins (e.g., temporin B + L mixtures permeabilize E. coli outer membranes cooperatively) has been documented in the family, but CDYe alone likely lacks this reach.
Why it matters
Establishing the Gram-negative activity boundary defines the clinical niche (Gram-positive skin/wound infections versus broad-spectrum) and points toward rational pairing with outer-membrane permeabilizers to expand spectrum.
Plausibility.52
Novelty.18
Impact.50
Basis · grounding2 papers · 1 computed/note
[1]
sequenceCandidate mature peptide EVKVEEKRFIGPIISALASLFGG has a short cationic N-terminus before a long hydrophobic stretch, limiting its ability to self-penetrate LPS layers.
[2]
paper
Temporin family members typically show limited Gram-negative activity unless combined; cited in selectivity axis for this card.
doi: 10.1016/j.peptides.2003.12.003
[3]
paper
Temporin-SHd/SHe time-kill kinetics tested against both S. aureus and E. coli, illustrating family-wide Gram-negative weakness as a reference benchmark.
doi: 10.3390/ijms21186713
openupdated 2026-06-05

Does this peptide kill bacteria by punching through their outer layer rather than hitting a specific target inside?

Bacteria rapidly evolve resistance to drugs that block specific internal targets, but physically destroying a membrane is much harder to evolve around. If this mode of action is confirmed, it would support the case that this class of peptides could stay effective longer than conventional antibiotics, which is important for anyone facing recurring or hard-to-treat bacterial infections.

The hypothesis
The mature region of Temporin-CDYe (approximately EVKVEEKRFIGPIISALASLFGG) kills Gram-positive bacteria primarily by forming amphipathic alpha-helices that disrupt the cytoplasmic membrane rather than by targeting an intracellular macromolecule, and this membrane-disruption mode is driven by the hydrophobic FIGPIISALASLFGG stretch.
Why it’s plausible
Temporins as a family are classically membrane-disrupting peptides. The candidate mature sequence contains an N-terminal cationic patch (EVKVEEKR) for initial electrostatic docking onto anionic bacterial membranes, followed by a highly hydrophobic run (FIGPIISALASLFGG) that would insert into the lipid bilayer. The absence of a C-terminal disulfide ring (Rana box) distinguishes this from brevinins and removes a constraint that might redirect the mode of action. The axis hits for mechanism cite temporin membrane interaction literature directly (10.1016/j.peptides.2003.12.003).
Why it matters
A confirmed membrane-disruption mechanism supports low likelihood of resistance development and motivates formulation strategies that preserve the peptide's amphipathic fold at the target surface.
Plausibility.52
Novelty.13
Impact.42
Basis · grounding2 papers · 1 computed/note
[1]
sequenceEVKVEEKR is an N-terminal cationic anchor; FIGPIISALASLFGG is a contiguous hydrophobic helix-forming segment; no cysteine pair for a Rana box.
[2]
paper
Temporin family members B and L act by direct membrane disruption; cited in mechanism axis hits for this card.
doi: 10.1016/j.peptides.2003.12.003
[3]
paper
Source paper places the peptide in the temporin family from R. dybowskii, consistent with membrane-active AMPs.
doi: 10.1016/j.cbpb.2009.05.015
details expand to inspect
full evidence table1 metrics
metricvaluetool
ranking score 0.6178147196769714 boltz-2
3-letter notation
Met-Phe-Thr-Leu-Lys-Lys-Ser-Met-Leu-Leu-Leu-Leu-Phe-Leu-Gly-Thr-Ile-Ser-Leu-Thr-Leu-Cys-Glu-Glu-Glu-Arg-Asp-Ala-Asn-Glu-Glu-Glu-Glu-Asn-Gly-Gly-Glu-Val-Lys-Val-Glu-Glu-Lys-Arg-Phe-Ile-Gly-Pro-Ile-Ile-Ser-Ala-Leu-Ala-Ser-Leu-Phe-Gly-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). Temporin-CDYe antimicrobial peptide (pep-05503, v1). PeptideModel. https://peptidemodel.com/card/pep-05503
@peptide{pep05503,
  sequence = {MFTLKKSMLLLLFLGTISLTLCEEERDANEEEENGGEVKVEEKRFIGPIISALASLFGG},
  target   = {antimicrobial},
  author   = {peptidemodel},
  year     = {2026},
  status   = {computed}
}
related peptides 2 by signal overlap
references 1 papers
[1]
Characterization of antimicrobial peptides isolated from the skin of the Chinese frog, Rana dybowskii
Jin L; Li Q; Song S; Feng K; Zhang D; Wang Q; Chen Y Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology 2009
source scaffold
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