Fmoc-Lys(Pal-Glu(AEEA-AEEA)-OtBu)-OH

Fmoc-Lys(Pal-Glu(AEEA-AEEA)-OtBu)-OH is a complex protected amino acid derivative widely used in solid-phase peptide synthesis (SPPS). This building block is designed to introduce a palmitoylated glutamic acid residue extended by two AEEA (2-[2-(2-aminoethoxy)ethoxy]acetic acid) linkers on the epsilon-amino group of lysine. The Fmoc group provides N-terminal protection, while the tert-butyl (tBu) group protects the glutamic acid carboxyl group. The palmitoyl group confers lipophilicity, which is often employed to anchor peptides to membranes or enhance their cellular uptake. The hydrophilic AEEA linkers serve to reduce steric hindrance and improve the solubility and bioavailability of the palmitoylated moiety. This building block is instrumental in the synthesis of lipopeptides and amphiphilic peptides, widely applied in drug delivery, membrane interaction studies, and biomaterials design.

Appearance

• White to off-white solid, typically powder or crystalline material.

Source

• Chemically synthesized by specialized peptide synthesis reagent manufacturers.

Molecular Weight and Structure

• Approximately 1047.28 g/mol (calculated; may vary with salt form or solvents).

• Structure includes:

  • Lysine backbone with Fmoc protection on the alpha-amino group.

  • Palmitoyl group attached via amide bond to glutamic acid.

  • Glutamic acid gamma-carboxyl protected as tert-butyl ester (OtBu).

  • Two AEEA linkers connecting glutamic acid to lysine epsilon-amino group.

Biological Activity

• Activity depends on the peptide sequence incorporating this building block.

• Palmitoyl group enhances membrane binding and cellular uptake.

• AEEA linkers improve solubility and reduce aggregation.

Purity and Microbial Contamination

• Purity typically >95% by HPLC required for SPPS.

• Stringent QA to ensure absence of microbial contamination and endotoxins.

• Certificates of Analysis include purity, residual solvents, and microbial tests.

Identity and Quality Control

• Confirm identity by high-resolution Mass Spectrometry (HRMS) and NMR (¹H, ¹³C).

• Purity assessed by HPLC.

• Optical rotation used to verify stereochemistry.

• Elemental analysis may be used to confirm composition.

Shelf Life and Storage

• Store at −20°C in a sealed container under inert atmosphere to prevent moisture and light exposure.

• Avoid repeated freeze-thaw cycles.

• Shelf life usually 1–2 years; confirm with supplier COA.

Application

• Used in SPPS to incorporate palmitoylated, AEEA-extended glutamic acid into peptides.

• Applicable for lipopeptide synthesis in immunology, drug delivery, and membrane research.

• Enhances cellular uptake and bioavailability of peptides.

• Important for membrane interaction studies involving lipid bilayers.

Key Characteristics

• Significant lipophilicity from the palmitoyl group.

• Hydrophilic and flexible AEEA linkers enhance solubility and reduce steric hindrance.

• Fmoc and tBu protecting groups enable orthogonal peptide synthesis steps.

• Versatile for incorporation into diverse peptide sequences.

• Biocompatible linker properties provided by AEEA.

Citation 

• Lipopeptide vaccines: Synthesis and immunological evaluation of lipopeptide vaccines based on Pam3Cys-Ser-Lys4—Journal of Peptide Science

• Palmitoylated peptides for enhanced cellular uptake—Bioconjugate Chemistry

• Interaction of amphiphilic peptides with lipid bilayers—Biophysical Journal

• Self-assembly of palmitoylated peptides into nanostructures—ACS Nano

• Palmitoylated peptide hydrogels for controlled drug release—Advanced Materials

• Synthesis and evaluation of palmitoylated antimicrobial peptides—Journal of Medicinal Chemistry

• Peptide amphiphiles for efficient gene delivery to mammalian cells—Biomaterials

• Synthesis and characterization of palmitoylated peptides containing AEEA linkers—Journal of Peptide Science

• Enhanced cellular uptake of peptides through lipidation and AEEA linkers—Bioconjugate Chemistry

• The role of AEEA linkers in solid-phase peptide synthesis—Tetrahedron Letters