Lipid modification of proteins plays a significant role in cellular signals’ activation and drug delivery system for anchoring the protein on a carrier. Thus, the artificial synthesis of lipidated proteins has been developed, however, getting a high yield and purity of lipidated proteins has been challenging. Herein, we demonstrate a strategy for modifying proteins with a wide variety of synthetic lipids (fatty acids, tocopherol, lithocholic acid, cholesterol) using microbial transglutaminase (MTG). MTG catalyzes the cross-linking reaction between a specific glutamine (Q) in a protein and lysine (K) in the lipid-fused peptide. Synthesized lipid-G3S- MRHKGS lipids as MTG substrates was successfully conjugated to a protein fused with LLQG (Q-tagged protein) by an MTG reaction, yielding &gt; 90% conversion of the Q-tagged protein into a lipidated form. The purified lipid-protein conjugates were applied for labeling the cell membrane in vitro, resulting in best-anchoring ability of cholesterol modification. Furthermore, in situ cell-surface decoration with the protein was achieved in a simple manner: subjection of cells to a mixture of cholesterol-G3S-MRHKGS, Q-tagged proteins and MTG.

Transglutaminase-mediated lipid bilayer decoration with proteins using lipid-fused peptide amphiphile substrates

2019 Fall National Meeting

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