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Lipid modification of proteins through sortase-catalyzed transpeptidation.

ABSTRACT: A general chemoenzymatic method for the site-specific attachment of lipids to protein substrates is described. Sortase A is used to append short lipid-modified oligoglycine peptides to the C terminus of protein substrates bearing a five amino acid sortase A recognition sequence (LPETG). We demonstrate the attachment of a range of hydrophobic modifications in excellent yield (60-90%), including a simple step for removing the sortase enzyme postreaction. Lipoproteins prepared using these procedures were subsequently shown to associate with mammalian cells in a lipid tail-dependent fashion and localized to the plasma membrane and endosomes.

SUBMITTER: Antos JM

PROVIDER: S-EPMC2647021 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Lipid modification of proteins through sortase-catalyzed transpeptidation.

Antos John M JM Miller Gwenn M GM Grotenbreg Gijsbert M GM Ploegh Hidde L HL

Journal of the American Chemical Society 20081201 48

A general chemoenzymatic method for the site-specific attachment of lipids to protein substrates is described. Sortase A is used to append short lipid-modified oligoglycine peptides to the C terminus of protein substrates bearing a five amino acid sortase A recognition sequence (LPETG). We demonstrate the attachment of a range of hydrophobic modifications in excellent yield (60-90%), including a simple step for removing the sortase enzyme postreaction. Lipoproteins prepared using these procedure ...[more]

PMID: 18989959

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