LAH4 peptide

• Handling and Storage of Synthetic Peptides
• Material Safety Data Sheets (MSDS)

Batch to batch variation of the purity

LAH4 is a 26-amino-acid cationic amphipathic α-helical peptide (sequence: KKALLALALHHLAHLALHLALALKKA), carrying a net charge of +5 at neutral pH thanks to 5 lysines and 4 histidines. It has a hydrophobic moment of 1.35 and average hydrophobicity of 1.28, and can bind nucleic acids spontaneously.

Its conformation changes with pH: at pH 7.5, terminal lysines anchor it across lipid bilayers as a transmembrane helix; in acidic environments, histidine imidazole groups get protonated, flipping LAH4 to lie flat on the membrane surface. Solid-state NMR confirms LAH4 preferentially binds and disturbs the acyl chains of anionic lipids (PS, PG), barely affecting neutral phosphatidylcholine (PC), and this lipid-disrupting effect intensifies under acid conditions.

The peptide’s membrane-damaging potency is controlled by the spatial angle of positively charged histidines: variants with 80° or 100° histidine angles break anionic lipid structures most effectively, while 60° and 180° variants work poorly.

Multiple modified LAH4 derivatives (LAH4-L1, LAH4-L1-R, LAH4-Leu, LAH4-L1-Leu, LAH4-L1-F) are created via amino acid substitutions. These changes adjust peptide hydrophobicity and hydrophobic moment, tuning their binding to nucleic acids and cell membranes, and all LAH4-type peptides break endosomal membranes in a pH-responsive way to deliver nucleic acids into cells.

• Mason AJ, Martinez A, Glaubitz C, Danos O, Kichler A, Bechinger B. The antibiotic and DNA-transfecting peptide LAH4 selectively associates with, and disorders, anionic lipids in mixed membranes. FASEB J. 2006 Feb;20(2):320-2. doi: 10.1096/fj.05-4293fje. Epub 2005 Dec 13. PMID: 16352649.
• Langlet-Bertin B, Leborgne C, Scherman D, Bechinger B, Mason AJ, Kichler A. Design and evaluation of histidine-rich amphipathic peptides for siRNA delivery. Pharm Res. 2010 Jul;27(7):1426-36. doi: 10.1007/s11095-010-0138-2. PMID: 20393870.

Trifluoroacetic acid (TFA) is a common counterion from the purification process using High-Performance Liquid Chromatography (HPLC). The presence of TFA can affect the peptide's net weight, appearance, and solubility.

Impact on Net Weight: The TFA salt contributes to the total mass of the product. In most cases, the peptide content constitutes >80% of the total weight, with TFA accounting for the remainder.

Solubility: TFA salts generally enhance the solubility of peptides in aqueous solutions.

In Biological Assays: For most standard in vitro assays, the residual TFA levels do not cause interference. However, for highly sensitive cellular or biochemical studies, please be aware of its presence.