N2-(1-Oxotetradecyl)-L-lysyl-L-alanyl-L-lysyl-L-alaninamide
[CAS# 959610-24-3]

Identification

• Classification: Biochemical >> Peptide
• Name: N2-(1-Oxotetradecyl)-L-lysyl-L-alanyl-L-lysyl-L-alaninamide
• Synonyms: N-[(2S)-6-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]tetradecanamide
• Protein Sequence: KAKA
• Molecular Formula: C₃₂H₆₃N₇O₅
• Molecular Weight: 625.89
• CAS Registry Number: 959610-24-3
• SMILES: CCCCCCCCCCCCCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N

Properties

• Solubility: Very slightly soluble (0.17 g/L) (25 ºC), Calc.^*
• Density: 1.060±0.06 g/cm³ (20 ºC 760 Torr), Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2015 ACD/Labs)

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P305+P351+P338

Discovory and Applicatios

N2-(1-Oxotetradecyl)-L-lysyl-L-alanyl-L-lysyl-L-alaninamide is a synthetic tetrapeptide characterized by a lipid-modified N-terminal lysine residue and amidation at the C-terminal alanine. The addition of a 1-oxotetradecyl group introduces a long-chain fatty acid moiety, enhancing the compound’s amphiphilic character and potentially increasing membrane affinity and biological stability. Such modifications are commonly employed in peptide chemistry to improve peptide–membrane interactions, bioavailability, and resistance to enzymatic degradation.

The discovery and design of lipidated peptides like N2-(1-Oxotetradecyl)-L-lysyl-L-alanyl-L-lysyl-L-alaninamide emerged from studies in the late twentieth century exploring peptide therapeutics and functional biomolecules. Researchers recognized that conjugation of fatty acid chains to short peptides could significantly alter pharmacokinetic and pharmacodynamic properties, enabling applications in drug delivery, antimicrobial activity, and receptor targeting. By combining amino acid sequences with lipid moieties, chemists could engineer molecules with tailored solubility, stability, and cellular uptake.

Structurally, the tetrapeptide contains lysine residues with positively charged side chains at physiological pH, which can facilitate interactions with negatively charged cellular surfaces or biomolecules. Alanine residues provide hydrophobicity and conformational flexibility, stabilizing the backbone and influencing secondary structure. The N-terminal oxotetradecyl group increases hydrophobic surface area, promoting interaction with lipid bilayers and potentially enhancing membrane penetration. The amidated C-terminal alanine improves chemical stability by reducing susceptibility to carboxypeptidase cleavage.

Applications of N2-(1-Oxotetradecyl)-L-lysyl-L-alanyl-L-lysyl-L-alaninamide are primarily in biochemical research and experimental therapeutics. Lipidated peptides of this type have been studied as potential antimicrobial agents, exploiting their amphiphilic nature to interact with and disrupt microbial membranes. Additionally, such peptides can be used as model compounds to investigate peptide–lipid interactions, membrane binding dynamics, and structure–activity relationships in modified peptides. Their stability and defined sequence make them useful tools for mechanistic studies in cellular and molecular biology.

From an analytical perspective, the peptide serves as a standard for method development in chromatographic and spectrometric analyses. Its well-defined molecular structure, combined with lipidation, provides predictable behavior in separation techniques and mass spectrometry, facilitating quantification and structural verification. The presence of the long-chain acyl group may also be exploited to study partitioning and binding in lipid-based systems.

Although N2-(1-Oxotetradecyl)-L-lysyl-L-alanyl-L-lysyl-L-alaninamide is primarily used as a research tool, its design reflects broader strategies in peptide therapeutics, where lipidation is employed to improve bioavailability, enhance tissue targeting, or modulate biological activity. Such modifications illustrate how chemical engineering of short peptide sequences can create molecules with properties distinct from their unmodified counterparts.

Overall, N2-(1-Oxotetradecyl)-L-lysyl-L-alanyl-L-lysyl-L-alaninamide exemplifies the integration of amino acid sequence design and lipid modification to produce stable, functional peptides. Its structural features, including basic residues, hydrophobic alanine units, N-terminal lipidation, and C-terminal amidation, make it a versatile compound for studying peptide–membrane interactions, evaluating enzymatic stability, and exploring the potential of amphiphilic peptides in biochemical research.

References

2025. Nanoparticle dispersions comprising therapeutic agents. WO Patent.
URL: WO-2024112807-A1

2025. Nanoparticle dispersions comprising therapeutic agents. EP Patent.
URL: EP-4622671-A1