Enzymatic cell-surface decoration with a functional protein using amphiphilic lipid-fused peptide substrates

摘要

Lipid-modification of proteins plays a significant role in regulating cellular signals on the cell-membrane. Thus, lipidated protein has been in demand, however, the synthesis of lipidated protein with high yield is still challenging because of the hydrophobic lipid moiety. Herein, we developed an enzymatic strategy of modifying proteins efficiently with wide variety of synthetic lipids. The specific enzyme is microbial transglutaminase (MTG) that proceeds the cross-linking reaction between specific glutamine (Q) in a protein and lysine (K) in lipid-fused peptides. As MTG-reactive K substrates, we newly synthesized lipid-G3S-MRHKGS (lipid: C12, C14, C16, C18, tocopherol, lithocholic acid, cholesterol, Figure a) whose amphiphilic property rendered water-solubility without any additives.