GALA 

GALA is a pH-responsive amphipathic peptide consisting of 30 amino acids, which acts as a lung endothelium-targeting ligand. GALA undergoes a conformational transition from random coil to α-helix in an acidic environment at pH 5.0, thereby inducing endosomal membrane destabilization and fusion. GALA-modified liposomes traverse lung endothelial cells via clathrin-dependent endocytosis and transcytosis, and specifically accumulate in the lungs after intravenous injection. GALA significantly promotes the cytosolic release of cargos carried by exosomes, plasmids and liposomes, effectively enhances gene transfection efficiency, and drives gene knockdown of functional macromolecules (such as siRNA) in alveolar epithelial cells (with no significant cytotoxicity at effective concentrations). GALA serves as a critical tool for studies on lung cancer metastasis (e.g., melanoma lung metastasis) and lung-targeted drug delivery systems^[1][2][3].

GALA/Chol-LPs (11-55 nmole lipids; 2-3 h) are mainly internalized by human lung microvascular endothelial cells (HMVEC-L) via the clathrin-mediated endocytosis pathway. After 3 h of incubation, 14 μM Chlorpromazine (HY-12708) inhibits its uptake by 52%^[1].
When combined with exosomes not expressing CD63-GFP and Lipofectamine LTX, GALA peptide (0.5-2 μM; 37 °C; 6 h) exhibits enhanced cellular uptake efficiency and cytosolic distribution levels in HeLa cells, with 2 μM GALA increasing the cellular uptake level by approximately 12-fold^[2].
When used in combination with Lipofectamine LTX, GALA peptide (2-10 μM; 37 °C; 6 h) increases the cellular uptake of CD63-GFP-expressing exosomes in HeLa cells by approximately 1.5-fold at a concentration of 2 μM, while 10 μM GALA peptide reduces the uptake efficiency^[2].
When used in combination with Texas red (HY-101878)-labeled dextran-encapsulated exosomes and Lipofectamine LTX, GALA peptide (0.5-2 μM; 37 °C; 6 h) drives efficient cytosolic release of dextran in HeLa cells, with 2 μM GALA inducing cytosolic dextran signals in approximately 60% of cells^[2].
Co-treatment with the GALA peptide (2 μM; 37 °C; 24 h), saporin-loaded exosomes and Lipofectamine LTX induces approximately 98% death of HeLa cells, and exerts potent cytotoxicity by enhancing the cytoplasmic delivery of saporin^[2].
GALA (0.1-5.0 μM; 12-48 h) enhances Lipofectin-mediated luciferase transfection efficiency in COS-7 cells in a concentration-dependent manner. Specifically, treatment with 0.1 μM GALA for 48 h increases the transfection efficiency by 5-fold, and GALA enhances the transfection efficiency by approximately 3.5-fold at all tested time points (12, 24, 48 h)^[3].
GALA (0.1-5.0 μM; 48 h) enhances the luciferase transfection efficiency mediated by Lipofectamine 2000 in COS-7 cells, with a 2-fold increase in transfection efficiency observed after treatment with 0.1 μM GALA for 48 h^[3].
GALA (0.1 μM; 5 h) does not alter the cellular localization of rhodamine-labeled plasmid DNA in Lipofectin-transfected COS-7 cells, but it colocalizes with the plasmid in vesicles and exhibits diffuse cytoplasmic staining^[3].
GALA (0.1 μM; 5 h) reduces cellular uptake of rhodamine-labeled plasmid DNA in COS-7 cells transfected with cationic liposomes, with the greatest reduction (approximately 19%) observed when Lipofectin is used^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

GALA-modified liposomes (26.4 nmol lipids/kg; i.v.; single dose) accumulate extensively in mouse lung endothelial cells, with >70% of endothelial cells taking up the particles, and cross the endothelial barrier to reach ~30-35% of type I alveolar epithelial cells^[1].
GALA/Chol-MEND and GALA/PEG2000-MEND (1.5 mg siRNA/kg; i.v.; single dose) achieve significant gene silencing in mouse type I alveolar epithelial cells, reducing podoplanin mRNA expression by 29% and 24%, respectively^[1].
GALA/Chol-MEND (2 mg AuNPs/kg; i.v.; single dose) crosses the mouse lung air-blood barrier, delivering gold nanoparticles to lung endothelial cells, alveolar epithelial cells, and alveolar macrophages^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

3032.36

C₁₃₆H₂₁₅N₃₃O₄₅

107658-43-5

Solid

White to off-white

Trp-Glu-Ala-Ala-Leu-Ala-Glu-Ala-Leu-Ala-Glu-Ala-Leu-Ala-Glu-His-Leu-Ala-Glu-Ala-Leu-Ala-Glu-Ala-Leu-Glu-Ala-Leu-Ala-Ala

WEAALAEALAEALAEHLAEALAEALEALAA

Room temperature in continental US; may vary elsewhere.

Sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

• [1]. Santiwarangkool S, et al. A study of the endocytosis mechanism and transendothelial activity of lung-targeted GALA-modified liposomes. J Control Release. 2019;307:55-63.  [Content Brief]

  [2]. Nakase I, et al. Combined treatment with a pH-sensitive fusogenic peptide and cationic lipids achieves enhanced cytosolic delivery of exosomes. Sci Rep. 2015;5:10112. Published 2015 May 26.  [Content Brief]

  [3]. Futaki S, et al. Unique features of a pH-sensitive fusogenic peptide that improves the transfection efficiency of cationic liposomes. J Gene Med. 2005;7(11):1450-1458.  [Content Brief]