Lipid-protein conjugates not only regulate cellular functions but also serve for drug delivery by their affinity toward albumin and lipoproteins in blood serum. Thus, artificial synthesis of lipid-protein conjugates has been required, however, hydrophobicity of lipid moiety makes the synthesis challenging without denaturing proteins. Herein, we focused on the site-specific ligation of a protein and lipopeptides using microbial transglutaminase (MTG). The enzymatic reaction of MTG is cross-linking between glutamine (Q) and lysine (K) residues in biomolecules. As our designed lipopeptide substrates, lipid-G<sub>3</sub>S-RHK peptides were employed for MTG-mediated protein lipidation, yielding &gt;90% conversion rates of a model protein fused with MTG-reactive LLQG sequence. The obtained lipopeptide-protein conjugates were evaluated for <i>in vitro</i> cell adhesion ability and albumin interaction, showing that choresterol modification rendered the protein with best cell adhesion efficiency and albumin affinity.

Enzymatic labeling of a protein with lipopeptides for albumin interaction

ACS Fall 2020 Virtual Meeting

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