Protegrin
A potent pig white-blood-cell antimicrobial peptide — a rigid disulfide beta-hairpin that kills drug-resistant bacteria by punching pores. Research compounds, not drugs
Protegrin is one of the most potent antimicrobial peptides known, and it comes from the white blood cells of pigs. It belongs to the cathelicidin family — the same innate-immune family as the human peptide LL-37 — but structurally it looks like the horseshoe-crab peptide tachyplesin: a short, strongly cationic beta-hairpin locked into shape by two disulfide bonds. That rigid, charged structure lets protegrin bind and punch pores in microbial membranes, and protegrin-1 (PG-1), the best-studied member, is broadly active against Gram-positive and Gram-negative bacteria, fungi and even some enveloped viruses, including many drug-resistant hospital pathogens. It also binds bacterial endotoxin and tempers inflammation. The catch — as with other powerful membrane-active peptides — is that PG-1 is strongly damaging to red blood cells, which is why most translational work uses engineered, less-toxic analogs; the best known of these, IB-367 (iseganan), reached clinical trials. Protegrins are research peptides; they are not approved medicines and have not been given to people as an approved treatment.
No established human dose Details ↓
Recommended Dosing
No established human dose
Protegrins are pig research peptides; no protegrin is an approved treatment. Even the clinically tested analog iseganan is investigational.
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What is it?
Pigs defend themselves with some remarkably potent antimicrobial peptides, and the protegrins, first described in 1993 from pig white blood cells, are the standouts. They belong to the cathelicidin family of host-defence peptides, but their shape is that of a beta-hairpin: two short strands folded back on each other and pinned by two disulfide bonds, the same rigid architecture seen in the horseshoe-crab peptide tachyplesin. The best-characterized member, protegrin-1 (PG-1), is only eighteen residues, strongly cationic, and amidated at its C-terminus. The family runs from protegrin-1 to protegrin-5.
Protegrin's mechanism is pore formation: the cationic hairpin binds the anionic surface of a microbial membrane, inserts, and assembles into pores that permeabilise the cell. This makes PG-1 broadly and rapidly bactericidal against Gram-positive and Gram-negative bacteria, fungi and some enveloped viruses, and — importantly — it stays effective against pathogens that resist last-resort antibiotics. Recent work shows PG-1 kills colistin-resistant Klebsiella whose membranes are remodelled to repel the antibiotic colistin, and a deep mutational scan of its triple-arginine loop found that subtle, position-specific changes to the hairpin's structure matter as much as net charge for keeping that activity. Against carbapenem-resistant Pseudomonas, adding the chelator EDTA (and chitosan) restored and boosted PG-1's activity even in serum.
Beyond direct killing, protegrin-1 is an immune modulator. As a cathelicidin it binds bacterial lipopolysaccharide (endotoxin) and neutralises it, dampening the over-activation of macrophages, and it can influence how immune cells handle bacteria and even intracellular parasites. In a mouse model of multidrug-resistant porcine extraintestinal E. coli infection, PG-1 improved survival, cut bacterial loads across organs and calmed the hyper-inflammatory response (NF-kB, MAPK and TNF signalling) — combining resistance-proof killing with a restoration of immune balance.
The family's great strength is also its central problem: PG-1's pore-forming power extends to host cells, making it strongly hemolytic, which has kept the natural peptide out of the clinic. The route forward has been engineering. Computational and synthetic studies have produced PG-1 analogs with much lower red-blood-cell toxicity that keep membrane-disrupting potency and gain chemical stability, and a family of named analogs — IB-367 (iseganan), PLP-3, HV2 and CDP-1 — has been pursued for clinical use; iseganan in particular was developed as a topical antimicrobial and taken into human trials. These are research and investigational compounds, not treatments given to people as approved drugs.
Through all of this, protegrins remain research peptides. No protegrin is an approved medicine, and even the clinically tested analog iseganan is investigational; material sold online under these names is an unregulated research chemical. Nothing here is a dose or a therapy; this page records what the published science says.
Mechanism of Action
Protegrin is an ~18-residue cationic beta-hairpin pig white-blood-cell (cathelicidin) antimicrobial peptide, stabilised by two disulfide bonds, that permeabilises microbial membranes by forming pores — broad-spectrum and fast, including against drug-resistant bacteria. It also binds endotoxin and modulates immunity; it is strongly hemolytic, so safer analogs (including iseganan) are engineered.
Pig-white blood cell host defense
An ~18-residue cationic beta-hairpin stabilised by two disulfide bonds, from porcine white blood cells; a cathelicidin, with members PG-1 to PG-5 (PMIDs 39094445, 42019271).
Pore-forming membrane disruption
Binds and permeabilises microbial membranes by forming pores (bacteria, fungi, some viruses), staying active against colistin- and carbapenem-resistant pathogens (PMIDs 42207438, 42019271).
Endotoxin binding, immunomodulation, engineering
Neutralises lipopolysaccharide and tempers inflammation; strongly hemolytic, so analogs (IB-367/iseganan, PLP-3, PEP-D) are engineered for safety (PMIDs 39094445, 40143068).
Published Research
These are studies of protegrins read from their PubMed records on November 7, 2026: PG-1 (with EDTA) against carbapenem-resistant Pseudomonas; a deep mutational scan of PG-1's arginine loop against colistin-resistant Klebsiella; a mouse study of PG-1 against multidrug-resistant E. coli with immunomodulation; a review of PG-1 and its analogs; PG-1's antimicrobial and immunomodulatory (endotoxin-neutralising) activities; and a design study of less-hemolytic PG-1 analogs. The evidence is in bacteria, cells and animals; no protegrin is an approved treatment.
EDTA restores protegrin-1 activity against resistant Pseudomonas in serum
The chelator EDTA fully restored the antimicrobial activity of protegrin-1 (and the pig peptide PR-39) against carbapenem-resistant Pseudomonas aeruginosa in serum, where peptide activity is usually blunted, and adding chitosan boosted it further — supporting a combined peptide/EDTA/chitosan platform (an in-vitro study).
The arginine loop governs protegrin-1 activity against colistin-resistant Klebsiella
A deep mutational scan of protegrin-1's triple-arginine loop against colistin-resistant Klebsiella pneumoniae showed that a single arginine-to-proline change in the strand-to-turn region cut activity even with disulfide bonds intact, and that removing two loop arginines abolished it — demonstrating that position-specific structure matters as much as net charge for penetrating resistant membranes (an in-vitro study).
Protegrin-1 against multidrug-resistant E. coli in mice
Against a multidrug-resistant porcine extraintestinal E. coli strain, protegrin-1 was potently bactericidal, induced no resistance over repeated passages, and in a mouse infection model improved survival, reduced bacterial loads in multiple organs and tempered the hyper-inflammatory response (NF-kB, MAPK, TNF signalling) — combining direct killing with immunomodulation (a preclinical study).
Protegrin-1 and its analogues: a review
A review summarises protegrin-1 as one of the most promising antimicrobial peptides, with broad Gram-positive and Gram-negative activity (including Acinetobacter baumannii) and synergy with antibiotics such as colistin, while noting that its hemolytic risk means clinical use is most likely through less-toxic analogs such as PLP-3, HV2, CDP-1 and IB367 (a review).
Antimicrobial and immunomodulatory activities of protegrin-1
Protegrin-1 neutralised bacterial lipopolysaccharide and dampened endotoxin- and bacteria-induced activation of macrophages by blocking LPS attachment, influenced how macrophages handled bacteria, and inhibited the survival of intracellular Leishmania parasites in macrophages — extending its protective role beyond direct antibacterial killing (an in-vitro study).
Designing less-hemolytic protegrin-1 analogs
From twelve computationally screened protegrin-1 analogs, three were synthesised and tested; the best (PEP-D) matched PG-1's charge and hydrophobicity, killed bacteria by disrupting membranes with significantly reduced red-blood-cell toxicity, and was chemically stable for six months — showing how PG-1 can be redesigned toward a safer anti-infective (an in-vitro study).
No Established Human Dose
Protegrins are pig research peptides; no protegrin is an approved treatment. Even the clinically tested analog iseganan is investigational. The work here is in bacteria, cultured cells and animals, often with engineered analogs, at experimental amounts that do not carry over to people, so no amount is printed here.
What this rests on: PMID 42207438, PMID 41295668, PMID 39288825.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Protegrin is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of Protegrin has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Protegrin, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Protegrin stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Protegrin. What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
How long it stays in the body: a half-life of not established for humans; a disulfide-stabilised beta-hairpin, more protease-resistant than linear AMPs. After about five half-lives almost none is left.
When effects appear: unknown; no source on this page gives a time to effect for Protegrin. Results reported in the studies are under Published Research.
Source: half-life: PMID 39288825.
Side effects, and when to stop or get help
From the Side Effects section: No approved-treatment human safety data exist for protegrin itself (the analog iseganan was tested clinically but is not approved); Protegrin-1 is strongly hemolytic (damaging to red blood cells) and cytotoxic to host cells at active concentrations — the central safety concern, and the reason less-toxic analogs are engineered (PMIDs 39288825, 40143068) — research findings, not approved-drug data; It binds and neutralises endotoxin and modulates immune cells (PMID 39094445), effects to weigh in any development; Material sold online as a 'protegrin' is an unregulated research chemical of unverified content. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Protegrin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Protegrins are research peptides and no protegrin is an approved treatment, so there is no established human safety profile; the points below reflect that status and their biology”).
Interactions
Unknown: a PubMed search for human interaction studies of Protegrin (reviewed 2026-11-07) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Protegrin products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not approved drugs: Drugs@FDA and the openFDA label endpoint hold no record, and FDA GSRS and ChEMBL hold no approved-drug record for protegrin peptides (searched November 7, 2026)). Sport: Not on the 2026 List.
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
Protegrins are research peptides and no protegrin is an approved treatment, so there is no established human safety profile; the points below reflect that status and their biology.
Contraindications & Cautions
Protegrins have no approved use and no label. These points reflect their research status.
Legal Status
Protegrins are pig white-blood-cell antimicrobial peptides used as research compounds; they are not approved drugs in any country.
Frequently Asked Questions
?What is protegrin?
An antimicrobial peptide from pig white blood cells, in the cathelicidin family. Protegrin-1 (PG-1) is an 18-amino-acid cationic beta-hairpin held by two disulfide bonds, first described in 1993; the family runs PG-1 to PG-5 (PMID 42019271).
?How does it work?
It binds and permeabilises microbial membranes by forming pores, with broad, rapid activity against bacteria (including drug-resistant ones), fungi and some viruses; it also binds endotoxin and modulates immunity (PMIDs 42207438, 39094445).
?What is iseganan?
Iseganan (IB-367) is an engineered, less-toxic protegrin-1 analog that was developed as a topical antimicrobial and taken into human clinical trials; it is investigational, not an approved drug (PMID 40143068).
?Is it approved or available to buy?
No. Protegrins are not approved medicines, have no FDA application or label, and are approved nowhere (iseganan is investigational). Material sold online as a protegrin is an unregulated research chemical. Grey Peptides lists no sellers and recommends no source; this page records the published science.
References
- [mechanism] Vacek L, et al. "EDTA enhances antimicrobial activity of PR-39 and Protegrin-1 antimicrobial peptides against carbapenem-resistant Pseudomonas aeruginosa in serum." Folia Microbiol (Praha), 2026;71(5):1485-1493. PMID: 42207438.
- [mechanism] DeBarro C, et al. "Local structural constraints and charge distribution in the protegrin-1 arginine loop govern activity against colistin-resistant Klebsiella pneumoniae." Drug Resist Updat, 2026;87:101405. PMID: 42019271.
- [animal] Xu J, et al. "Protegrin-1 Combats Multidrug-Resistant Porcine ExPEC: Potent Bactericidal Activity and Multimodal Immunometabolic Regulation In Vitro and in a Murine Model." Vet Sci, 2025;12(11). PMID: 41295668.
- [review] Rizzetto G, et al. "Protegrin-1 and Analogues Against Acinetobacter baumannii: A Narrative Review." Pharmaceuticals (Basel), 2025;18(3). PMID: 40143068.
- [mechanism] Javed A, et al. "Antimicrobial and immunomodulatory activities of porcine cathelicidin Protegrin-1." Mol Immunol, 2024;173:100-109. PMID: 39094445.
- [mechanism] Hosseini Goki N, et al. "Novel antimicrobial peptides based on Protegrin-1: In silico and in vitro assessments." Microb Pathog, 2024;196:106931. PMID: 39288825.
- [other] Protegrins are beta-hairpin antimicrobial peptides from porcine (pig) white blood cells, members of the cathelicidin family, first described by Kokryakov, Lehrer and colleagues (FEBS Lett, 1993), who noted that they combine features of defensins and the horseshoe-crab tachyplesins. The family includes protegrin-1 through protegrin-5; their structure and activities are described in the studies carded on this page (read November 7, 2026).
- [other] US FDA, Drugs@FDA and the openFDA label endpoint, searched November 7, 2026: no application and no label record for protegrin peptides. They are pig research antimicrobial peptides, not approved drugs; FDA GSRS and ChEMBL hold no approved-drug record for them.
Sources & Citations
The six studies carded above were read from their PubMed records on November 7, 2026. Protegrin's pig white-blood-cell (cathelicidin) origin, its ~18-residue two-disulfide beta-hairpin structure, its pore-forming membrane mechanism and activity against drug-resistant bacteria, its endotoxin-neutralising and immunomodulatory activity, and its strong hemolysis and the engineered analogs (including iseganan) made to reduce it are from the studies carded here; the discovery is Kokryakov, Lehrer et al. (FEBS Lett, 1993). The absence of US approval or a drug record from Drugs@FDA, openFDA, FDA GSRS and ChEMBL was checked the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.