title: Palmitoylated SDF1α shows increased resistance against proteolytic degradation in liver homogenates.
abstract: The chemokine stromal cell-derived factor-1α (SDF1α) is strongly involved in organogenesis, as well as inflammation and tissue repair, and acts by attracting different kinds of stem and progenitor cells. Therefore, it constitutes an interesting compound for drug development in regenerative medicine. However, it is prone to inactivation by proteolytic cleavage in human serum. Accordingly, it has to be stabilized against enzymatic degradation for any therapeutic application. We synthesized a palmitoylated SDF1α analogue by native chemical ligation. Both the N-terminal thioester and the C-terminal palmitoylated fragment were prepared by solid-phase peptide synthesis. The activity of the refolded and pure compound was determined by an inositol phosphate turnover assay and revealed no loss in receptor activation. Additionally, resistance to proteolytic degradation was investigated in porcine liver homogenates and showed a near sevenfold increased half time. This study is a proof of principle approach for the lipidation of SDF1α and provides a basis for further engineering of the chemokine in order to increase its therapeutic value.
authors.affiliation: Institute of Biochemistry, Leipzig University, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Bellmann-Sickert
authors.forename: Annette G
authors.initials: AG
authors.lastname: Beck-Sickinger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D054377:Chemokine CXCL12 / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D002522:Chlorocebus aethiops; D006207:Half-Life; D006801:Humans; D007295:Inositol Phosphates / Q000032:analysis; D054878:Lipoylation; D008099:Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000378:metabolism; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism*; D044968:Regenerative Medicine; D013552:Swine
chemical_list: D054377:Chemokine CXCL12; D007295:Inositol Phosphates; D019718:Receptors, CXCR4; D010447:Peptide Hydrolases