Synthesis of granulocyte–macrophage colony-stimulating factor as homogeneous glycoforms and early comparisons with yeast cell-derived material

Granulocyte–macrophage colony-stimulating factor (GM-CSF) is a medicinally important glycoprotein, used as an immunostimulant following bone-marrow transplant. On the basis of reports of its potential utility as an anticancer vaccine adjuvant, we undertook to develop a synthetic route toward single-...

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Bibliographic Details
Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 8; pp. 2885 - 2890
Main Authors:	Zhanga, Qiang, Johnstona, Eric V., Shiehb, Jae-Hung, Mooreb, Malcolm A. S., Danishefsky, Samuel J.
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 25-02-2014 National Acad Sciences
Subjects:	Alanine - chemistry Amino Acid Sequence Bone marrow Cell lines Chemical synthesis Colony stimulating factors Congeners Cysteine - chemistry Escherichia coli Glycoproteins Glycosylation Granulocyte-Macrophage Colony-Stimulating Factor - chemical synthesis Ligation Medical treatment Models, Molecular Molecular Sequence Data Molecular Structure Physical Sciences Polysaccharides Protein Conformation Synthetic materials Transplants & implants Vaccination Vaccines glycoprotein synthesis alanine ligation peptide ligation
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Summary:	Granulocyte–macrophage colony-stimulating factor (GM-CSF) is a medicinally important glycoprotein, used as an immunostimulant following bone-marrow transplant. On the basis of reports of its potential utility as an anticancer vaccine adjuvant, we undertook to develop a synthetic route toward single-glycoform GM-CSF. We describe herein a convergent total synthesis of GM-CSF aglycone and two homogeneous glycoforms. Analytical and biological studies confirm the structure and activity of these synthetic congeners.
Bibliography:	http://dx.doi.org/10.1073/pnas.1400140111 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 Author contributions: Q.Z., E.V.J., J.-H.S., M.A.S.M., and S.J.D. designed research; Q.Z., E.V.J., and J.-H.S. performed research; Q.Z., E.V.J., J.-H.S., M.A.S.M., and S.J.D. analyzed data; and Q.Z., E.V.J., J.-H.S., M.A.S.M., and S.J.D. wrote the paper. 1Q.Z. and E.V.J. contributed equally to this work. Contributed by Samuel J. Danishefsky, January 7, 2014 (sent for review December 18, 2013)
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.1400140111