R.O. gratefully acknowledges receipt of a JSPS Postdoctoral Fellowship for Research Abroad.
Total Chemical Synthesis and Biological Activities of Glycosylated and Non-Glycosylated Forms of the Chemokines CCL1 and Ser-CCL1†
Article first published online: 18 MAR 2014
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Volume 126, Issue 20, pages 5288–5293, May 12, 2014
How to Cite
Okamoto, R., Mandal, K., Ling, M., Luster, A. D., Kajihara, Y. and Kent, S. B. H. (2014), Total Chemical Synthesis and Biological Activities of Glycosylated and Non-Glycosylated Forms of the Chemokines CCL1 and Ser-CCL1. Angew. Chem., 126: 5288–5293. doi: 10.1002/ange.201310574
- Issue published online: 8 MAY 2014
- Article first published online: 18 MAR 2014
- Manuscript Received: 6 DEC 2013
- Chemische Proteinsynthese;
- Native chemische Ligation
CCL1 is a naturally glycosylated chemokine protein that is secreted by activated T-cells and acts as a chemoattractant for monocytes.1 Originally, CCL1 was identified as a 73 amino acid protein having one N-glycosylation site,1 and a variant 74 residue non-glycosylated form, Ser-CCL1, has also been described.2 There are no systematic studies of the effect of glycosylation on the biological activities of either CCL1 or Ser-CCL1. Here we report the total chemical syntheses of both N-glycosylated and non-glycosylated forms of (Ser-)CCL1, by convergent native chemical ligation. We used an N-glycan isolated from hen egg yolk together with the Nbz linker for Fmoc chemistry solid phase synthesis of the glycopeptide-αthioester building block.3 Chemotaxis assays of these glycoproteins and the corresponding non-glycosylated proteins were carried out. The results were correlated with the chemical structures of the (glyco)protein molecules. To the best of our knowledge, these are the first investigations of the effect of glycosylation on the chemotactic activity of the chemokine (Ser-)CCL1 using homogeneous N-glycosylated protein molecules of defined covalent structure.