DOPE‑Maleimide (DOPE‑Mal)

Key Properties

• Chemical Structure: A reactive phospholipid conjugate consisting of 1,2‑dioleoyl‑sn‑glycero‑3‑phosphoethanolamine (DOPE) linked to a maleimide (Mal) functional group, often via a hydrophilic PEG spacer.
• Amphiphilicity: Combines the hydrophobic lipid tails of DOPE for membrane insertion with a reactive maleimide head group for bioconjugation.
• Thiol‑Specific Reactivity: The maleimide moiety undergoes highly selective, covalent Michael addition with thiol (‑SH) groups (e.g., on cysteine residues) at physiological pH (6.5–7.5), forming stable thioether bonds.
• Membrane Fusion & Phase Behavior: Retains the inherent fusogenic and pH‑sensitive properties of DOPE, promoting endosomal escape and non‑bilayer phase transitions.
• Solubility: Soluble in organic solvents (chloroform, DMSO, ethanol); PEG‑containing variants exhibit improved aqueous solubility.
• Physical Form: Typically a white to off‑white solid or waxy material.
• Molecular Formula: C₄₈H₈₃N₂O₁₁P
• Molecular Weight: 895.15 g/mol

Applications

• Targeted Liposome & LNP Functionalization: Covalently anchors thiol‑containing targeting ligands (antibodies, peptides, aptamers) to lipid bilayer surfaces for cell‑specific delivery.
• Gene & Nucleic Acid Delivery: Used in cationic liposome/LNP formulations to enhance intracellular delivery of DNA, mRNA, and siRNA, leveraging DOPE’s fusogenicity.
• Protein & Peptide Conjugation: Enables site‑specific coupling of proteins/peptides to lipid assemblies for theranostic applications.
• Stealth & Long‑Circulating Systems: When PEGylated (DOPE‑PEG‑Mal), it reduces non‑specific protein adsorption and extends blood circulation half‑life.
• Biomembrane Modeling: Serves as a building block for artificial cell membranes and biosensor interfaces.
• Fluorescent/Probe Labeling: Conjugates with thiolated dyes or radionuclides for in vitro/in vivo imaging and tracking.