Larazotide acetate is a synthetic octapeptide, sequence Gly-Gly-Val-Leu-Val-Gln-Pro-Gly, developed as an antagonist of the zonulin pathway that regulates intestinal tight junctions — and it is unusual among research peptides in having reached phase 3 clinical investigation, in celiac disease, before development ended. Two things set it apart from almost everything else in a peptide catalogue: it is designed to act locally in the gut lumen rather than systemically, and its target is a structural feature of epithelium rather than a hormone receptor.
This page covers the origin of the sequence, the tight-junction biology it was built to interrogate, what has been published, and how the material is supplied and handled. Larazotide acetate is stocked in an oral capsule format for laboratory research use only; nothing here is guidance for administration to humans or animals.
Larazotide acetate at a glance
| Property | Value |
|---|---|
| Sequence | Gly-Gly-Val-Leu-Val-Gln-Pro-Gly (GGVLVQPG) |
| Length | 8 residues (octapeptide) |
| Also known as | AT-1001; INN larazotide |
| Salt form | Acetate |
| CAS number | 881851-50-9 |
| Molecular formula | C32H55N9O10 |
| Molecular weight | 725.90 g/mol |
| Target pathway | Zonulin-mediated tight junction disassembly |
| Design intent | Luminal action at the epithelial surface; minimal systemic absorption |
| Format supplied | Oral capsules, 500 mcg per capsule, 30 and 60 counts |
| Purity specification | ≥99% by RP-HPLC with lot-matched COA |
Origin and structure: from a bacterial toxin to an eight-residue antagonist
The lineage of larazotide begins with Vibrio cholerae. Alongside cholera toxin, the organism produces zonula occludens toxin, ZOT, which opens intestinal tight junctions and was studied in the 1990s as a tool for probing paracellular permeability. Work on ZOT led to the identification of a human counterpart — zonulin, subsequently characterised as pre-haptoglobin-2 — that appears to regulate junctional opening physiologically.
Larazotide was derived from that work as a short peptide designed to oppose junctional disassembly rather than to induce it. At eight residues and 725.90 g/mol it is a small, uncharged, largely aliphatic sequence with a single glutamine and a proline that constrains the backbone. It carries no aromatic residues, no cysteines and no ionisable side chains beyond the termini, which makes it chemically undemanding to synthesise and stable to handle — a stark contrast with a molecule such as LL-37.
The design choice that most affects how it is studied is its intended pharmacokinetics: it is meant not to be absorbed. Systemic exposure is a liability rather than an objective, because the target sits at the apical surface of the epithelium. That inverts the usual optimisation problem for peptide research and explains why the product exists as a capsule rather than a lyophilized vial.
How larazotide is thought to work
Tight junctions are multiprotein complexes — occludin, claudins, junctional adhesion molecules and the cytoplasmic ZO scaffolding proteins — that seal the space between adjacent epithelial cells and determine paracellular permeability. They are dynamic: signalling through protein kinase C and reorganisation of the perijunctional actomyosin ring can loosen them in a regulated way.
Zonulin is proposed to trigger that loosening, and larazotide is described in the literature as an antagonist of the pathway. The mechanisms reported include interference with actin polymerisation and myosin light chain phosphorylation at the perijunctional ring, with the consequence that tight junction proteins remain assembled rather than being displaced from the junction. Note the framing carefully: it is not described as tightening healthy junctions but as blocking a disassembly signal. That distinction predicts the pattern seen in the literature, where effects are reported in systems where a permeability challenge has been applied rather than in unchallenged monolayers.
It is worth adding that the zonulin story itself remains debated. The identification of pre-haptoglobin-2 as zonulin and the assay methods used to measure it have both been questioned in the literature, and a careful researcher should treat the pathway as an active hypothesis rather than settled physiology.
What research has examined
Intestinal permeability in vitro
The standard system is a polarised epithelial monolayer, typically Caco-2, with transepithelial electrical resistance and labelled-marker flux as readouts, often after a challenge such as gliadin digest or a cytokine. Immunofluorescence for occludin, claudins and ZO-1 shows whether junctional proteins remain at the membrane.
Animal models
Rodent work has examined permeability markers and mucosal architecture in models of gluten sensitivity and of chemically induced barrier disruption.
Human clinical investigation
Larazotide is one of the very few peptides in this catalogue with a substantial trial record. Multiple phase 2 studies were conducted in celiac disease in patients maintaining a gluten-free diet, with symptom scores as endpoints; results across those studies were mixed, with some reporting benefit at particular exposures. A phase 3 programme followed and was discontinued in 2022 after an interim analysis, and the compound has never received marketing authorisation anywhere. That history is genuinely useful context: it is an example of a peptide with real human data that nonetheless did not become a medicine.
Barrier research beyond the gut
Because the pathway is of interest wherever barrier integrity matters, the peptide also appears in exploratory work on other epithelial and endothelial barriers. This literature is small.
Forms and sizes we supply
Because the design intent is luminal action, larazotide acetate is supplied as oral capsules at 500 micrograms per capsule in 30-count (USD 85) and 60-count (USD 150) bottles, with a tamper-evident seal and desiccant. Fill weight consistency matters more in this format than in a vial, because the capsule is the unit of measurement. Related oral research material includes BPC-157 capsules and KPV capsules, and the whole gut-directed group sits under gut health peptides. The general problem of getting peptides through the gastrointestinal tract intact is covered in our guide to oral peptides, capsules and troches.
Handling and storage in a laboratory context
Capsules require no reconstitution, which removes the usual arithmetic. For in-vitro work, capsule contents can be weighed and dissolved; a 500 microgram unit dissolved in 1 mL gives 500 mcg/mL, equivalently 0.5 mg/mL, which at 725.90 g/mol is approximately 689 micromolar. Published monolayer studies typically operate several orders of magnitude below that, so serial dilution is required and the excipient content of the capsule should be accounted for when precise concentrations are needed — for that work, weighing pure peptide is preferable to using capsule contents.
Bottles are kept closed, cool, dry and out of light with the desiccant left in place; humidity, not temperature, is the main enemy of a capsule format. The peptide itself is chemically robust, having no cysteine, methionine or asparagine-glycine motif to worry about. General principles are in the peptide storage guide.
Purity, COA and how to read one
The peptide is purified by reversed-phase HPLC to at least 99% before encapsulation, with a certificate matched to the lot number on the bottle. Two points are specific to this material. First, the salt form is part of the identity: larazotide acetate means the peptide is supplied as an acetate salt, not a TFA salt, and the certificate should say so — acetate is generally preferred where residual trifluoroacetate would interfere with cell work. Second, in a capsule format the certificate covers the peptide, while fill weight and content uniformity are separate manufacturing attributes; both matter if the capsule is the unit of measurement. Confirm the observed mass against 725.90 g/mol for the free peptide and read the chromatogram rather than the headline number, as set out in our COA reading guide.
Regulatory status
Larazotide holds no marketing authorisation in the United States or elsewhere. Its phase 3 programme in celiac disease was discontinued, and it is not an approved drug, a dietary supplement ingredient or a generally available compounded medication. Material supplied here is research use only, for laboratory investigation by qualified researchers, and is not intended for human or veterinary administration. Published clinical data describe an investigational product studied under controlled conditions and do not transfer to research-grade material.
Related peptides and further reading
Within gut-directed research, KPV approaches epithelial inflammation through NF-kappa B signalling and BPC-157 through repair and angiogenic mechanisms, so the three cover different points in the same physiology. For a survey of the whole area, see the peptides for gut health research overview and the institutional gut and enteric system hub.