Larazotide: Molecular Structure

Molecular Structure and Properties#

Larazotide acetate is a synthetic octapeptide with the sequence Gly-Gly-Val-Leu-Val-Gln-Pro-Gly (GGVLVQPG). It has a molecular weight of approximately 785.9 Da, molecular formula C34H59N9O12, and CAS number 881851-50-9 (acetate salt). The peptide is highly polar and acts locally in the gastrointestinal lumen with minimal systemic absorption.

Amino Acid Sequence#

The primary structure is an 8-residue linear peptide:

H-Gly-Gly-Val-Leu-Val-Gln-Pro-Gly-OH

Key features:

• All L-amino acids: Standard configuration without non-natural residues
• Hydrophobic core: Val-Leu-Val at positions 3-5 provide a hydrophobic segment
• Proline at position 7: Introduces a backbone bend that may be important for receptor binding conformation
• Terminal glycines: Flexible termini that do not contribute to steric specificity

Origin: Zonula Occludens Toxin#

Larazotide is derived from the zonula occludens toxin (Zot) of Vibrio cholerae. Zot is a 44.8 kDa bacterial protein that activates the zonulin pathway to increase intestinal permeability, facilitating cholera toxin entry. Larazotide corresponds to a fragment of Zot that retains receptor binding but has been modified to act as an antagonist rather than an agonist, blocking zonulin-mediated tight junction opening.

Pharmacokinetics#

Larazotide has an unusual pharmacokinetic profile for a therapeutic peptide:

• Route: Oral administration (capsule)
• Systemic absorption: Minimal; the peptide acts locally within the gut lumen
• Distribution: Primarily confined to the gastrointestinal tract
• Metabolism: Expected to be degraded by gastrointestinal peptidases
• Half-life: Not clinically relevant as the drug acts locally

The lack of systemic absorption is therapeutically advantageous because it minimizes the potential for systemic side effects. The peptide binds to zonulin receptors on the luminal surface of intestinal epithelial cells before being degraded by digestive enzymes.

Physicochemical Properties#

• Solubility: Highly soluble in aqueous solutions due to the polar amino acid composition
• Stability: Formulated as oral capsules; specific stability data not publicly disclosed
• Oral bioavailability: Low systemic bioavailability by design; the active site is the gut lumen
• Formulation: Administered as larazotide acetate in oral capsule form

Molecular Context#

Larazotide belongs to the Immune category of research peptides. The molecular properties of Larazotide determine its pharmacological behavior, including receptor binding, distribution, metabolism, and elimination. Understanding these properties is fundamental to interpreting clinical data and designing research protocols.

Structural Overview#

Larazotide is characterized as: Synthetic octapeptide derived from Vibrio cholerae zonula occludens toxin; zonulin receptor antagonist that prevents tight junction opening.

Amino Acid Sequence Details#

The amino acid sequence of Larazotide is: H-Gly-Gly-Val-Leu-Val-Gln-Pro-Gly-OH (GGVLVQPG). This sequence determines the peptide's three-dimensional structure, receptor binding properties, and biological activity.

Pharmacokinetic Profile#

Half-Life: Not applicable -- larazotide acts locally in the gut lumen with minimal systemic absorption

The half-life of a peptide influences dosing frequency, duration of effect, and the clinical utility of the compound. Researchers should consider the half-life when designing experimental protocols.

Related Reading#

• Larazotide overview and research guide
• Peptides similar to Larazotide
• Larazotide research evidence