AEEA-AEEA

AEEA-AEEA is a hydrophilic, biocompatible linker composed of two units of 2-[2-(2-aminoethoxy)ethoxy]acetic acid (AEEA) joined together. This dimer provides an extended and flexible spacer arm compared to a single AEEA, enhancing solubility, reducing steric hindrance, and improving bioavailability when conjugated to biomolecules. It is commonly used in bioconjugation and peptide synthesis to increase the distance between functional groups or conjugated molecules, facilitating more efficient ligand binding and better biological performance, especially in vivo.

Appearance

• Clear, colorless to slightly yellow liquid or white to off-white solid

• Typically hygroscopic

Source

• Chemically synthesized and commercially available from specialized chemical suppliers and bioconjugation reagent manufacturers such as Sigma-Aldrich, Thermo Fisher Scientific, and Iris Biotech

• Less common than single AEEA, custom synthesis may be required

Molecular Weight

• 322.34 g/mol

Structure

• HOOC-CH₂-O-CH₂-CH₂-O-CH₂-CH₂-NH-CO-CH₂-O-CH₂-CH₂-O-CH₂-CH₂-NH₂

Biological Activity

• Generally biologically inert and highly biocompatible

• Enhances solubility, bioavailability, and target interactions of conjugated molecules through its extended hydrophilic structure

Purity and Microbial Contamination

Shelf Life and Storage

• Store at -20°C in dry, inert atmosphere (argon or nitrogen)

• Protect from light and moisture

• Shelf life typically 1–2 years under proper storage conditions

Application

• Peptide synthesis: introduces longer, hydrophilic spacers into peptides

• Bioconjugation: links biomolecules, drugs, and imaging agents to surfaces, nanoparticles, or other molecules requiring extended spacing

• Polymer chemistry: monomer or building block for hydrophilic, flexible polymers

• Surface modification: enhances hydrophilicity and functionality of surfaces

• Drug delivery: improves solubility, bioavailability, and circulation time of conjugated drugs

Key Characteristics

• Hydrophilic ethylene glycol-based backbone

• Biocompatible and non-toxic

• Flexible, reduces steric hindrance

• Bifunctional with amine and carboxylic acid end groups

• Extended linker length improves spatial separation of conjugates

Citation

• “The Use of AEEA Linkers to Modulate the Solubility and Aggregation of Amyloid-β Peptides.” ACS Chemical Neuroscience, 2013

• “Solid-phase synthesis of constrained peptides using AEEA as a linker.” Tetrahedron Letters, 2006

• “Site-Specific PEGylation of Proteins Using AEEA Linkers.” Bioconjugate Chemistry, 2010

• “AEEA-based dendrimers for enhanced drug delivery.” Journal of Controlled Release, 2015

• “AEEA-modified surfaces for reduced protein adsorption.” Langmuir, 2012

• “AEEA-functionalized gold nanoparticles for sensitive biosensing.” Biosensors and Bioelectronics, 2018

• “AEEA-containing hydrogels for cell encapsulation.” Biomacromolecules, 2014

• “Synthesis and properties of peptide nucleic acids containing AEEA linkers.” Nucleic Acids Research

• “AEEA spacer enhances conjugation efficiency of antibodies to nanoparticles.” Bioconjugate Chemistry

• “AEEA-modified imaging probes for improved tumor penetration and targeting.” Molecular Imaging