pe
pep-05687 v1 CC-BY-SA-4.0

Cathelicidin antimicrobial peptide

A naturally occurring germ-killing peptide that kills bacteria or stops them from growing; used only as a lab research tool.

statuscomputed targetANTIMICROBIAL length54 aa refs1
antibacterialantimicrobial
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
pTM0.460
avg pLDDT66.6
ranking score0.625
STRUCTURE · PEP-05687 × ANTIMICROBIAL
ranking0.625
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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
sequence54 aa
1510152025303540455054
LLGDFFRKSKEKIGKEFK RIVQRIKDFLRNLVPRTE SDYKDDDDKCQDSERTFY
in the news 6 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 2026-06-11

Does the acidic FLAG tag attached to this peptide's tail cut its germ-killing power compared with the tag-free version?

If true, removing the tag could uncover a much more potent antibiotic peptide, giving researchers a stronger starting point for drug development. Patients with drug-resistant infections could eventually benefit from leads that were being artificially weakened.

The hypothesis
The DYKDDDDKCQDSERTFY C-terminal extension in pep-05687 is an intact FLAG purification tag fused to an LL-37-derived core, and this acidic tag (net -4 charge from DDDD) substantially neutralizes the cationic amphipathic core, reducing membrane disruption potency relative to untagged LL-37 variants by at least 4-fold in minimum inhibitory concentration assays against Gram-negative bacteria.
Why it’s plausible
The sequence DYKDDDDK is the canonical FLAG octapeptide used for affinity purification. Its four consecutive aspartates introduce strong negative charge that opposes the cationic N-terminal cathelicidin region (8+ from Arg/Lys). Charge neutralization is a well-established mechanism for reducing AMP membrane affinity. The surface-modification literature snippet is consistent with a tagged construct designed for immobilization rather than free activity.
Why it matters
If the FLAG tag is artifactually reducing potency, the intrinsic activity of the cathelicidin core is being systematically underestimated, and removal of the tag or substitution with a neutral linker could reveal the peptide's true therapeutic ceiling.
Plausibility.82
Novelty.60
Impact.65
Basis · grounding1 paper · 1 computed/note
[1]
sequenceResidues 44-51 spell DYKDDDDK, the canonical FLAG affinity tag, introducing 4 Asp anions into an otherwise cationic cathelicidin scaffold.
[2]
paper
Literature context involves surface-attached AMPs, consistent with a FLAG-tagged construct designed for solid-phase capture or oriented immobilization.
doi: 10.1016/j.actbio.2016.12.047
openupdated 2026-06-11

Does the charge-lowering tag on this peptide make it better at killing Gram-positive bacteria while sparing Gram-negative ones?

A peptide with built-in Gram-selectivity could be useful for treating infections where you want to spare beneficial gut bacteria while targeting pathogens. This would matter for patients on long-term antibiotic therapy.

The hypothesis
The intact FLAG-tagged pep-05687 retains membrane-disruptive activity against Gram-positive bacteria (which tolerate less cationic selectivity) more than against Gram-negative bacteria, because the reduced net cationic charge specifically impairs traversal of the Gram-negative outer membrane lipopolysaccharide barrier, creating an unintentional Gram-selectivity shift.
Why it’s plausible
Gram-negative bacteria require highly cationic AMPs to displace divalent cations from LPS and penetrate the outer membrane. Reducing net charge via the DDDD motif would specifically impair this electrostatic displacement step. Gram-positive bacteria lack the outer membrane, so amphipathic helix insertion into the cytoplasmic membrane is less charge-dependent. The cathelicidin N-terminal core (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRT) retains amphipathic helix potential.
Why it matters
If confirmed, the FLAG-tagged construct is an inadvertent tool for studying charge-versus-amphipathicity contributions to Gram-selectivity, with implications for rationally engineering narrow-spectrum AMPs.
Plausibility.70
Novelty.65
Impact.60
Basis · grounding2 computed/notes
[1]
sequenceN-terminal core (residues 1-37) contains LLGDFFR and KSKEKIGKEFKRIVQRIK motifs consistent with amphipathic helix; C-terminal DYKDDDDK lowers overall cationic character.
[2]
structurepLDDT 66.6 indicates partial disorder, consistent with a structured amphipathic N-terminal helix and a disordered/flexible C-terminal tag region.
openupdated 2026-06-11

Can this peptide's built-in tag be used to attach it to medical device surfaces in an orientation that keeps it active against bacteria?

If this works, catheters, implants, and surgical tools coated with this peptide could resist bacterial colonization without releasing antibiotics into the bloodstream. This could reduce healthcare-associated infections for thousands of patients annually.

The hypothesis
The FLAG-tag handle in pep-05687 enables oriented surface immobilization on anti-FLAG-coated biomaterials, and immobilized peptide retains sufficient amphipathic character to prevent bacterial biofilm formation, making this construct a ready-made dual-function coating agent combining purification convenience with contact-killing antimicrobial activity.
Why it’s plausible
The surface-modification literature directly motivates this hypothesis: attaching AMPs to surfaces via C-terminal affinity tags produces oriented layers where the active N-terminal domain faces outward. The cathelicidin core of pep-05687 (first 37 residues) has the amphipathic helix structure capable of membrane disruption even when the C-terminus is tethered, because the active face is not restrained.
Why it matters
Reframing this peptide as a surface-coating agent rather than a soluble drug could enable antimicrobial medical device coatings without the cytotoxicity concerns associated with high free-peptide concentrations.
Plausibility.70
Novelty.55
Impact.60
Basis · grounding1 paper · 1 computed/note
[1]
paper
The cited work explicitly addresses surface modification of polymers with antimicrobial peptides, directly motivating oriented FLAG-mediated immobilization of this construct.
doi: 10.1016/j.actbio.2016.12.047
[2]
sequenceDYKDDDDK at C-terminus positions the tag distal to the N-terminal amphipathic cathelicidin core, enabling oriented immobilization that leaves the active domain free.
openupdated 2026-06-11

Is this peptide less likely to burst human red blood cells than standard cathelicidin peptides, because of its acidic tail?

If this peptide is safer for human cells while still killing bacteria, it could be developed into a systemic antibiotic drug. Patients with bloodstream infections could benefit from a new class of treatment that avoids the toxicity problem that has blocked most AMP drugs.

The hypothesis
The chimeric charge profile of pep-05687 (cationic N-terminus, anionic C-terminus) confers reduced hemolytic activity compared to unmodified LL-37 at equimolar concentrations, because the intramolecular charge-charge repulsion between the DDDD region and cell-membrane phosphatidylserine reduces insertion depth into eukaryotic membranes.
Why it’s plausible
Hemolysis by cathelicidins correlates with net cationic charge and hydrophobicity. LL-37 itself has hemolytic liability at high doses. Reducing net charge by appending 4 Asp residues (as in the FLAG tag) has been documented to reduce red blood cell disruption for synthetic AMP analogues. The pep-05687 sequence preserves the hydrophobic LLGDFF and DFL motifs, making net-charge reduction the primary differentiator.
Why it matters
A less hemolytic cathelicidin variant with preserved antibacterial activity would have a wider therapeutic window, which is a major bottleneck in developing AMP-based systemic drugs.
Plausibility.58
Novelty.50
Impact.65
Basis · grounding1 computed/note
[1]
sequenceThe sequence contains DDDD from the FLAG tag (positions 45-48), adding 4 negative charges to a scaffold that would otherwise have ~10+ net charge, substantially narrowing the charge gap with eukaryotic membranes.
details expand to inspect
full evidence table1 metrics
metricvaluetool
ranking score 0.6249057650566101 boltz-2
3-letter notation
Leu-Leu-Gly-Asp-Phe-Phe-Arg-Lys-Ser-Lys-Glu-Lys-Ile-Gly-Lys-Glu-Phe-Lys-Arg-Ile-Val-Gln-Arg-Ile-Lys-Asp-Phe-Leu-Arg-Asn-Leu-Val-Pro-Arg-Thr-Glu-Ser-Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Lys-Cys-Gln-Asp-Ser-Glu-Arg-Thr-Phe-Tyr
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). Cathelicidin antimicrobial peptide (pep-05687, v1). PeptideModel. https://peptidemodel.com/card/pep-05687
@peptide{pep05687,
  sequence = {LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTESDYKDDDDKCQDSERTFY},
  target   = {antimicrobial},
  author   = {peptidemodel},
  year     = {2026},
  status   = {computed}
}
related peptides 1 by signal overlap
references 1 papers
[1] source scaffold
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