Design of Lipid-Protein Conjugates Using Amphiphilic Peptide Substrates of Microbial Transglutaminase

Mari Takahara, Rie Wakabayashi, Kosuke Minamihata, Masahiro Goto, Noriho Kamiya

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Lipid modification of proteins plays a significant role in regulating the cellular environment. Mimicking natural lipidated proteins is a key technique for assessing the function of proteins modified with lipids and also to render self-assembly of lipids to a target protein. Herein, we report a facile method of conjugating proteins with lipid-fused peptides under homogeneous physiological conditions by using the microbial transglutaminase (MTG) reaction. MTG catalyzes the cross-linking reaction between a specific glutamine (Q) in a protein and a lysine (K) in newly designed lipid-fused peptides. The water-soluble peptide substrates for lipid modification, C14-X-MRHKGS, were newly synthesized, where C14, X, and MRHKGS represent myristic acid, linker peptides composed of G, P, or S, and MTG-reactive K surrounded with basic amino acids, respectively. The MTG-mediated cross-linking reaction between a protein fused with LLQG at the C-terminus and C14-X-MRHKGS (5 molar eq) dissolved in a phosphate saline solution resulted in lipid-protein conjugates with yields of 70 to 100%. The anchoring ability of the obtained lipid-protein conjugates to cell membranes was dependent on the number of G residues in the GnS linker, suggesting that self-assembly and hydrophobicity of the GnS motif serves to enhance membrane anchoring of lipid-protein conjugates.

Original languageEnglish
Pages (from-to)1823-1829
Number of pages7
JournalACS Applied Bio Materials
Volume1
Issue number6
DOIs
Publication statusPublished - Dec 17 2018

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Transglutaminases
Lipids
Peptides
Proteins
Substrates
Cross Reactions
Self assembly
Basic Amino Acids
Myristic Acid
Cell membranes
Hydrophobicity
Membrane Lipids
Glutamine
Hydrophobic and Hydrophilic Interactions
Sodium Chloride
Lysine
Amino acids
Phosphates
Cell Membrane
Membranes

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Chemistry(all)
  • Biomedical Engineering
  • Biochemistry, medical

Cite this

Design of Lipid-Protein Conjugates Using Amphiphilic Peptide Substrates of Microbial Transglutaminase. / Takahara, Mari; Wakabayashi, Rie; Minamihata, Kosuke; Goto, Masahiro; Kamiya, Noriho.

In: ACS Applied Bio Materials, Vol. 1, No. 6, 17.12.2018, p. 1823-1829.

Research output: Contribution to journalArticle

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