pe
pep-05600 v1 CC-BY-SA-4.0

Krtap5-2 antibacterial peptide

A lab-made peptide that kills bacteria; used only as a research tool.

statusbioassayed targetANTIMICROBIAL length57 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 · 0 verified on platform
prediction metrics boltz-2 2.2.1
ipTM0.000
pTM0.497
avg pLDDT63.5
ranking score0.607
STRUCTURE · PEP-05600 × ANTIMICROBIAL
ranking0.607
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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
sequence57 aa
151015202530354045505557
CWSCMGHSCWSCMGHSCWS CAGHSCWSCMGHSCWSCMG HSCWSCAGHCCGSCWHGGM
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 peptide need to fold into a specific structure before it can fight infection?

If true, it would mean the peptide naturally spares human cells (which would quickly unfold it) while staying active in the oxidized environment outside bacteria. That built-in safety switch could make it easier and safer to use than older antibiotic compounds.

The hypothesis
The six cysteine-rich repeats of pep-05600 form an oxidized ladder of intramolecular disulfide bonds that adopts a beta-hairpin or ladder scaffold, and this oxidized form is the active bactericidal species while the reduced form is inactive.
Why it’s plausible
Keratin-associated proteins (Krtap) are hallmarked by extensive disulfide crosslinks that create rigid structural scaffolds in hair fibers. Pep-05600 is named after Krtap5-2, suggesting its sequence is derived from or mimics the cysteine-rich repeats of that protein. With ~32% Cys content, most cysteines must form disulfide bonds to avoid aggregation in aqueous conditions. If the disulfide-stabilized fold presents a positively charged or amphipathic face (the Trp and His residues interspersed among Cys), that folded state could be the membrane-active form. The reducing agent data from the Sonorensin reference (activity unaffected by reducing agents) would contrast with expected behavior if this hypothesis is correct for pep-05600.
Why it matters
Understanding whether the oxidized or reduced form is active directly governs formulation strategy: an oxidized active peptide requires redox-buffered storage and will be inactivated in highly reducing cytoplasmic environments, limiting cytotoxicity, which is favorable for selectivity.
Plausibility.65
Novelty.48
Impact.73
Basis · grounding1 paper · 1 computed/note
[1]
sequence~18 Cys in 57 residues; sequence name Krtap5-2 directly references a keratin-associated protein characterized by disulfide-crosslinked cysteine repeats
[2]
paper
Sonorensin activity was tested against reducing agents; data on reducing agent sensitivity contextualize disulfide dependence question for this structural class
doi: 10.1128/aem.04259-13
openupdated 2026-06-05

Could we chop most of this peptide away and still get the full antibacterial effect?

If the shorter version holds up, manufacturing costs could drop by roughly two-thirds. Lower cost is one of the main reasons promising antibiotic peptides never make it to patients, so this could meaningfully shorten the path from lab to clinic.

The hypothesis
Truncating pep-05600 to a minimal two-repeat unit (CWSCMGHSCWSCMGHSC, ~18 residues) retains full antibacterial potency while reducing synthesis cost and proteolytic vulnerability, because the repeat unit is the minimal pharmacophore.
Why it’s plausible
The sequence is built from five near-identical CWSCMGHSC repeats with Ala substituting Met at positions 3 and 6. The truncation precedent from Sonorensin-related peptides in the literature shows that P5 truncations retain activity. For a 57-residue peptide, solid-phase synthesis is near the cost-prohibitive length limit cited at 50 residues in the manufacturing axis. If two repeats are sufficient for the zinc-chelation or sortase-inhibition activity, cost per gram falls substantially and synthesis fidelity improves. The Ala variants suggest position 3 (Met to Ala) is already tolerated, informing mutagenesis space.
Why it matters
Reducing synthesis length from 57 to approximately 18 residues could cut manufacturing cost by two-thirds and dramatically improve scalability, which is identified as a primary barrier to AMP clinical translation in the manufacturing axis evidence.
Plausibility.52
Novelty.53
Impact.75
Basis · grounding2 papers · 1 computed/note
[1]
sequenceSequence is a five-fold repetition of CWSCMGHSC with two Ala substitutions at Met positions; minimal repeat unit is identifiable as CWSCMGHSC
[2]
paper
Solid-phase synthesis cost-prohibitive above 50 residues; truncation to sub-50-residue active fragments is a recognized strategy
doi: 10.1038/s41467-023-37003-z
[3]
paper
Truncated P5 peptide variants retain antibacterial activity, establishing truncation as a viable engineering approach for repeat-motif AMPs
doi: 10.1186/s13568-019-0843-0
openupdated 2026-06-05

Could this peptide be safe for human tissue while still being lethal to bacteria?

Most experimental antibiotic peptides are too toxic for the bloodstream because they punch holes in any cell they touch. If this one works by a different route that leaves human membranes alone, it might survive the safety hurdles that have blocked earlier antibiotic peptides from reaching patients.

The hypothesis
Pep-05600 has low mammalian cell toxicity relative to its antibacterial potency because its polyvalent cysteine scaffold preferentially coordinates free zinc in prokaryotic periplasm rather than disrupting eukaryotic membranes, and the peptide lacks the sustained positive charge density typical of membrane-lytic AMPs.
Why it’s plausible
Conventional lytic AMPs derive selectivity from the higher negative charge of bacterial membranes relative to mammalian ones; they require a net positive charge to insert. The pep-05600 sequence contains Met, Gly, Ala, Ser, Cys, His, and Trp but very few Lys or Arg residues, meaning net charge at physiological pH is near neutral or slightly negative once cysteines are oxidized. A near-neutral peptide would not drive electrostatic membrane insertion in either bacteria or mammalian cells, suggesting a non-lytic zinc-chelation or enzyme-inhibitory mode of selectivity.
Why it matters
If antibacterial activity is achieved without cationic membrane disruption, pep-05600 could have a safety window suitable for systemic use, unlike many first-generation cationic AMPs that failed clinical translation due to hemolysis and cytotoxicity.
Plausibility.53
Novelty.47
Impact.70
Basis · grounding1 paper · 1 computed/note
[1]
sequenceNo Lys or Arg residues identified in the full 57-residue sequence; near-neutral charge at physiological pH is inconsistent with cationic membrane-lytic mechanism
[2]
paper
Selectivity axis hit references AMP immune-defense roles, underscoring that non-lytic AMPs can achieve selectivity through non-membrane mechanisms
doi: 10.3389/fmicb.2022.888525
openupdated 2026-06-05

What if this peptide works like a zinc magnet that disarms bacteria rather than tearing them apart?

Bacteria evolve resistance to drugs by changing their outer membrane, but they cannot easily evolve around losing zinc from their core machinery. If this mechanism holds, the peptide could stay effective longer than conventional antibiotics, and might even work on dormant bacteria that are notoriously hard to kill.

The hypothesis
The dense tandem CWSCMGHSC repeats in pep-05600 enable zinc chelation from bacterial metalloenzymes, and zinc sequestration rather than membrane disruption is the primary bactericidal mechanism.
Why it’s plausible
The sequence contains approximately 18 cysteines and multiple histidines arranged in a CXXC...CXH pattern repeated five times. CXXC and CXH motifs are canonical zinc-coordination geometries found in zinc-finger domains and metallothioneins. Zinc is essential for multiple bacterial virulence enzymes and structural proteins. A peptide with this density of potential zinc ligands could strip zinc from bacterial targets faster than it disrupts membranes, especially since the reference bacteriocin context (Sonorensin, a heterocycloanthracin) includes metal-chelating activity in related compounds.
Why it matters
If the mechanism is metal chelation rather than membrane lysis, it fundamentally changes the resistance landscape: bacteria cannot easily evolve resistance by altering membrane composition, and the peptide would be active against non-replicating persister cells where membrane potential is low.
Plausibility.44
Novelty.53
Impact.73
Basis · grounding1 paper · 1 computed/note
[1]
sequenceCWSCMGHSC repeat unit contains CXXC and CXH zinc coordination motifs; ~18 Cys and ~6 His in 57 residues
[2]
paper
Reference bacteriocin Sonorensin inhibits L. monocytogenes and V. vulnificus at low MIC; heterocycloanthracins are known to interact with metal ions
doi: 10.1128/aem.04259-13
openupdated 2026-06-05

Could a single compound kill a dangerous bacterium and also block the enzyme that destroys surrounding tissue?

Vibrio vulnificus causes rapidly fatal wound infections, often progressing to limb loss or death within 48 hours. If this peptide can simultaneously eliminate the bacteria and neutralize the enzyme that destroys tissue, it could address both the infection and the spreading damage in a way no single current drug does.

The hypothesis
Pep-05600 is effective against Vibrio vulnificus wound infections because its Cys-His scaffold chelates the zinc metalloprotease VvpE, a key virulence factor in V. vulnificus necrotizing fasciitis, and this antivirulence activity synergizes with its direct bactericidal effect.
Why it’s plausible
The Sonorensin reference explicitly identifies V. vulnificus as one of the two most sensitive species. V. vulnificus causes rapidly progressing necrotizing fasciitis and septicemia with high mortality, and its primary virulence factor VvpE is a zinc-dependent metalloprotease with a catalytic zinc coordinated by HEXXH motif. A peptide with multiple Cys-His chelation units would be well-positioned to strip the catalytic zinc from VvpE. The co-occurrence of direct bactericidal activity and potential metalloprotease inhibition would make pep-05600 a dual-acting agent against this pathogen.
Why it matters
V. vulnificus infections are life-threatening within 24-48 hours and current antibiotic options are limited by rapid progression; a peptide that simultaneously kills the bacterium and neutralizes its tissue-destroying metalloprotease would address both the infection and the acute tissue damage, representing a meaningful clinical advance.
Plausibility.40
Novelty.55
Impact.77
Basis · grounding1 paper · 1 computed/note
[1]
paper
V. vulnificus is one of the two most sensitive species to Sonorensin, the reference compound for this peptide class; inhibited at lowest MIC values
doi: 10.1128/aem.04259-13
[2]
sequenceCWSCMGHSC repeats present Cys-His units capable of chelating the catalytic zinc of VvpE zinc metalloprotease (HEXXH active site)
details expand to inspect
full evidence table1 metrics
metricvaluetool
ranking score 0.6074571013450623 boltz-2
3-letter notation
Cys-Trp-Ser-Cys-Met-Gly-His-Ser-Cys-Trp-Ser-Cys-Met-Gly-His-Ser-Cys-Trp-Ser-Cys-Ala-Gly-His-Ser-Cys-Trp-Ser-Cys-Met-Gly-His-Ser-Cys-Trp-Ser-Cys-Met-Gly-His-Ser-Cys-Trp-Ser-Cys-Ala-Gly-His-Cys-Cys-Gly-Ser-Cys-Trp-His-Gly-Gly-Met
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). Krtap5-2 antibacterial peptide (pep-05600, v1). PeptideModel. https://peptidemodel.com/card/pep-05600
@peptide{pep05600,
  sequence = {CWSCMGHSCWSCMGHSCWSCAGHSCWSCMGHSCWSCMGHSCWSCAGHCCGSCWHGGM},
  target   = {antimicrobial},
  author   = {peptidemodel},
  year     = {2026},
  status   = {bioassayed}
}
references 1 papers
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