pe
pep-05511 v1 CC-BY-SA-4.0

Cathelicidin-6 antimicrobial peptide

A naturally occurring peptide that kills or slows the growth of bacteria and other microbes; used only as a lab research tool.

statuscomputed targetANTIMICROBIAL length59 aa refs3
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
pTM0.293
avg pLDDT48.5
ranking score0.447
STRUCTURE · PEP-05511 × ANTIMICROBIAL
ranking0.447
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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
LRVVDSLNQRSSDENLYRLL KLNSEPQGDENPNIPQPASF TVKETVCPKTTQQPLEQCD
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 2026-06-05

Could this peptide's real job be calming or directing the immune system rather than punching holes in bacterial membranes?

If the current label is wrong, researchers could stop pursuing dead-end antibacterial work and instead test whether this peptide could help treat inflammation, slow-healing wounds, or immune overreaction. Redirecting the science earlier saves years of effort and could open a more promising path to treatment.

The hypothesis
Pep-05511 does not function as a direct membrane-disrupting antimicrobial agent; its actual biological role is immunomodulatory, likely as a processed fragment of the cathelicidin pro-domain (cathelin domain) rather than the C-terminal active antimicrobial domain.
Why it’s plausible
The sequence carries a net charge of -3 at physiological pH (K+R count: 6, D+E count: 9), which is the opposite of all validated cathelicidin antimicrobial domains, which are strongly cationic (+4 to +9, e.g., LL-37 at +6). Additionally, six prolines (10.2% of residues) are distributed through the sequence, strongly disfavoring the amphipathic alpha-helix that is mechanistically required for membrane disruption. The Boltz-2 structure prediction returned an avg_pLDDT of 48.5 and ptm of 0.29, consistent with intrinsic disorder rather than the folded helical conformation of active cathelicidin AMPs. This charge and structural profile is instead characteristic of the conserved cathelin pro-domain, fragments of which have been shown to exert independent immunomodulatory activity. The annotation as an antimicrobial target is therefore likely a misclassification based solely on the cathelicidin-6 nomenclature rather than the actual sequence properties.
Why it matters
If correct, the card's primary annotation is wrong and all downstream work targeting membrane disruption would be misguided. Recharacterizing this as an immunomodulatory cathelin fragment would redirect development toward inflammation, wound healing, or innate immune priming rather than direct antibacterial applications.
Plausibility.81
Novelty.67
Impact.88
Basis · grounding2 papers · 3 computed/notes
[1]
sequenceNet charge -3 at pH 7 (K3, R3, D4, E5); all validated cathelicidin membrane-disrupting domains are cationic with net charge +4 to +9.
[2]
sequenceSix proline residues at positions 26, 32, 35, 37, 48, 54 (10.2%) preclude formation of an amphipathic alpha-helix.
[3]
structureavg_pLDDT of 48.5 and ptm of 0.29 indicate a highly disordered structure inconsistent with a folded helical AMP.
[4]
paper
Cathelicidins have a conserved cathelin pro-domain with independent immunomodulatory roles, distinct from the variable cationic C-terminal AMP domain.
doi: 10.1016/j.cellimm.2012.11.009
[5]
paper
Cathelicidin precursor architecture separates the pro-region (cathelin domain) from the functionally active C-terminal antimicrobial domain.
doi: 10.1016/j.gene.2011.11.009
openupdated 2026-06-05

Can this peptide intercept the bacterial toxin that hijacks the immune system and causes the runaway inflammation seen in sepsis?

If it turns out to work this way, this peptide could help reduce the catastrophic immune overreaction in sepsis patients without needing to kill bacteria directly. That might make it safer at lower doses and could offer doctors a new tool against one of the leading causes of death in intensive care units.

The hypothesis
Pep-05511 suppresses bacterial LPS-driven TLR4 signaling by competing with LPS for binding to MD-2, acting as a TLR4 antagonist rather than a direct bactericidal agent.
Why it’s plausible
Although the overall charge of pep-05511 is -3, the N-terminal 18 residues (LRVVDSLNQRSSDENLYR) carry a net neutral charge with three arginines (R2, R11, R18) that could engage the negatively charged lipid A region of LPS through arginine-phosphate interactions. The literature cites that some cathelicidins neutralize LPS by binding to it, a property not strictly dependent on net-cationic charge but on specific cationic patch geometry. The disordered nature of pep-05511 (pLDDT 48.5) could enable conformational adaptation to the hydrophobic pocket of MD-2. The proline-rich middle region and anionic C-terminus would help prevent deep membrane insertion while retaining the N-terminal arginine patch for LPS contact.
Why it matters
LPS neutralization that does not require membrane disruption would mean pep-05511 could dampen sepsis-associated TLR4 hyperactivation at concentrations below those causing host cytotoxicity, opening a path toward anti-sepsis therapeutics based on a mechanism distinct from conventional AMPs.
Plausibility.47
Novelty.58
Impact.67
Basis · grounding2 papers · 2 computed/notes
[1]
sequenceN-terminal region (aa 1-18): LRVVDSLNQRSSDENLYR, net charge 0 with 3 arginines at positions 2, 11, 18 forming a potential LPS-binding cationic patch.
[2]
paper
Cathelicidins are documented to modulate endotoxin signaling and structure-activity relationships for LPS binding are a recognized research focus.
doi: 10.1159/000174822
[3]
paper
Cathelicidin host defense peptides (CHDPs) modulate inflammation and link innate and adaptive immunity beyond direct microbial killing.
doi: 10.1038/s41573-019-0058-8
[4]
structureavg_pLDDT 48.5 (disorder) is consistent with adaptive binding mode required to fit the MD-2 hydrophobic cavity without preformed rigid structure.
openupdated 2026-06-05

Is there a short, looped piece of this peptide that does all the biological work, and does that work switch on or off depending on the body's chemical environment?

If the active part is just that small loop, chemists could build tiny, cheap copies of it rather than synthesizing the whole peptide. That could make any future drug based on this molecule far more practical and stable to produce.

The hypothesis
The C47-C58 disulfide bond in pep-05511 creates a constrained 12-residue loop (CPKTTQQPLEQC) that constitutes the biologically active structural unit, and oxidation state of this disulfide governs the peptide's immunomodulatory potency.
Why it’s plausible
The two cysteines at positions 47 and 58 are the only cysteines in the sequence, and they are separated by 10 residues. Formation of a C47-C58 disulfide would produce a compact loop containing PKTTQQPLEQ flanked by both cysteines. This loop is 25% glutamine and contains a KTTQ motif, which is structurally reminiscent of glutamine-rich cytokine-binding epitopes. The PLEQ sub-sequence in the loop has structural resemblance to cytokine receptor-binding turns. Critically, the peptide would present two very different conformational states depending on redox conditions: linear (reducing environment such as cytosol) versus looped (oxidizing environment such as extracellular space or phagolysosome). Since cathelicidins are concentrated in the phagolysosome (an oxidizing compartment), the disulfide-locked form would be the functionally relevant species in vivo.
Why it matters
If the disulfide loop is the active unit, short cyclic mimetics of CPKTTQQPLEQC could be synthesized as minimal pharmacophores, dramatically reducing the cost and improving the stability of any therapeutic derived from this sequence.
Plausibility.40
Novelty.58
Impact.55
Basis · grounding2 papers · 3 computed/notes
[1]
sequenceC47 and C58 are the only two cysteines in the 59-residue sequence; disulfide would close a 12-residue loop: CPKTTQQPLEQC.
[2]
sequenceThe loop contains 3 glutamines (25%), 2 threonines, and a KTTQ motif consistent with glutamine-rich cytokine-binding folds.
[3]
paper
Absence of disulfide bonds in some cathelicidins is noted as an advantage for synthesis, implying disulfide-containing variants have distinct structural constraints.
doi: 10.1016/j.bbamem.2009.08.021
[4]
paper
Cathelicidins in the phagolysosome are optimized for killing in a controlled oxidizing environment, relevant to disulfide formation context.
doi: 10.1038/s41573-019-0058-8
[5]
structureptm 0.29 and pLDDT 48.5 suggest the linear form is unstructured; disulfide-constrained loop could adopt a defined conformation not captured by the monomer prediction.
openupdated 2026-06-05

Could this peptide reduce the chronic gut inflammation that makes inflammatory bowel disease so difficult to manage?

Millions of people with IBD have few safe long-term options that do not broadly suppress the immune system. If this peptide can calm gut inflammation without wiping out protective immune responses or harming beneficial gut bacteria, it could offer a gentler maintenance therapy for people living with these conditions.

The hypothesis
Pep-05511 could reduce intestinal inflammation in inflammatory bowel disease (IBD) by modulating cathelicidin-related innate immune signaling in the gut epithelium.
Why it’s plausible
The cathelicidin family has a documented role in intestinal innate immunity and ulcerative colitis protection in mice (cited in the half-life axis hits). Pep-05511, with its anionic and disordered character, resembles the pro-domain fragments that modulate rather than kill, which could be particularly useful in IBD where excessive bactericidal activity can damage commensal microbiota. The literature excerpt from axis_hits (oral-bioavailability) specifically mentions cathelicidins protecting the urinary tract and a role in ulcerative colitis. The net-negative charge of pep-05511 would reduce non-specific toxicity to the zwitterionic outer leaflet of gut epithelial cells, while retaining immune-modulatory interactions through its arginine-containing N-terminal patch. The high proline content also confers relative resistance to gut proteases (proline is a poor substrate for most serine and cysteine proteases), suggesting partial oral bioavailability.
Why it matters
IBD lacks a safe, non-immunosuppressive maintenance therapy. A non-cytotoxic cathelicidin-derived peptide that modulates mucosal innate immunity without broadly suppressing adaptive immunity would address a significant unmet therapeutic need.
Plausibility.55
Novelty.30
Impact.55
Basis · grounding2 papers · 2 computed/notes
[1]
paper
Cathelicidins protect the urinary tract against invasive bacterial infection and have a documented role in ulcerative colitis in mouse models.
doi: 10.1097/moh.0b013e32831ac517
[2]
sequenceSix prolines (positions 26, 32, 35, 37, 48, 54) confer resistance to proline-intolerant gut proteases, suggesting partial proteolytic stability for oral or luminal administration.
[3]
sequenceNet charge -3 reduces electrostatic attraction to zwitterionic gut epithelial membranes, lowering cytotoxicity risk compared to cationic AMPs.
[4]
paper
Cathelicidins show selectivity between commensal bacteria and pathogens, important for IBD therapy where microbiome preservation is critical.
doi: 10.1038/s41573-019-0058-8
details expand to inspect
full evidence table1 metrics
metricvaluetool
ranking score 0.44689851999282837 boltz-2
3-letter notation
Leu-Arg-Val-Val-Asp-Ser-Leu-Asn-Gln-Arg-Ser-Ser-Asp-Glu-Asn-Leu-Tyr-Arg-Leu-Leu-Lys-Leu-Asn-Ser-Glu-Pro-Gln-Gly-Asp-Glu-Asn-Pro-Asn-Ile-Pro-Gln-Pro-Ala-Ser-Phe-Thr-Val-Lys-Glu-Thr-Val-Cys-Pro-Lys-Thr-Thr-Gln-Gln-Pro-Leu-Glu-Gln-Cys-Asp
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-6 antimicrobial peptide (pep-05511, v1). PeptideModel. https://peptidemodel.com/card/pep-05511
@peptide{pep05511,
  sequence = {LRVVDSLNQRSSDENLYRLLKLNSEPQGDENPNIPQPASFTVKETVCPKTTQQPLEQCD},
  target   = {antimicrobial},
  author   = {peptidemodel},
  year     = {2026},
  status   = {computed}
}
related peptides 5 by signal overlap
references 3 papers
[2] supporting
[3] supporting
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