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Synthetic glycopeptides as a designated standard in focused glycoproteomics to discover serum cancer biomarkers

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Abstract

Previous studies on the large-scale glycomics of more than 3500 human serum samples revealed that the serum glycoproteins of cancer patients often have more dominant and specific glycoforms, namely, branched tri- and tetra-antennary N-glycans, most cancer patient groups than normal control groups. We herein established an efficient synthetic protocol of glycopeptides having highly complicated N-glycan structures that may be generated by direct tryptic digestion of serum glycoproteins. A preliminary selected reaction monitoring (SRM) assay using the synthetic model glycopeptide 1, 40Ser-Val-Gln-Glu-Ile-Gln-Ala-Thr-Phe-Phe-Tyr-Phe-Thr-Pro-Asn-Lys-Thr-Glu-Asp-Thr-Ile-Phe-Leu-Arg63 having an asialo tri-antennary N-glycan at the Asn54 residue as a designated calibration standard allowed for the rapid and absolute quantitation of the tryptic fragment derived from the serum α1-acid glycoprotein carrying a focused N-glycoform of cancer patients and healthy controls in a range between 200 and 1600 fmole μL−1 without any enrichment process for the target glycoprotein.

Graphical abstract: Synthetic glycopeptides as a designated standard in focused glycoproteomics to discover serum cancer biomarkers

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Publication details

The article was received on 25 Mar 2018, accepted on 21 Jun 2018 and first published on 29 Jun 2018


Article type: Research Article
DOI: 10.1039/C8MD00162F
Citation: Med. Chem. Commun., 2018, Advance Article
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    Synthetic glycopeptides as a designated standard in focused glycoproteomics to discover serum cancer biomarkers

    K. V. Yogesh, T. Kamiyama, C. Ohyama, T. Yoneyama, K. Nouso, S. Kimura, H. Hinou and S. Nishimura, Med. Chem. Commun., 2018, Advance Article , DOI: 10.1039/C8MD00162F

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