title: Convergent Solid-Phase Synthesis of Macromolecular MUC1 Models Truly Mimicking Serum Glycoprotein Biomarkers of Interstitial Lung Diseases.
abstract: Synthetic macromolecular MUC1 glycopeptides have been used to unravel molecular mechanisms in antibody recognition of disease-specific epitopes. We have established a novel synthetic strategy for MUC1 tandem repeats having complex O-glycosylation states at each repeating unit based on convergent solid-phase fragment condensation under microwave irradiation. We have accomplished the synthesis of 77 amino acid MUC1 glycopeptides (MW = 12 759) having three major antigenic O-glycoforms [Tn, core 1 (T), and core 2 structures] at 10 designated positions out of 19 potential O-glycosylation sites. We demonstrate that the macromolecular MUC1 glycopeptide displaying the essential glycopeptidic neoepitope Pro-Asp-Thr(sialyl-T)-Arg-Pro-Ala-Pro at two different tandem repeats is an excellent serum MUC1 model showing ideal stoichiometric binding with anti-KL6/MUC1 antibody in the sandwich ELISA to quantify human serum KL6/MUC1 levels as a critical biomarker of interstitial lung diseases.
authors.affiliation: Shionogi & Company, Ltd. , 3-1-1 Futaba-cho, Toyonaka-shi, Osaka 561-0825, Japan.|Graduate School of Life Science and Faculty of Advanced Life Science, Hokkaido University , N21, W11, Kita-ku, Sapporo 001-0021, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ohyabu
authors.affiliation: Shionogi & Company, Ltd. , 2-1-3 Kuiseterashima, Amagasaki 660-0813, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kakiya
authors.affiliation: Graduate School of Life Science and Faculty of Advanced Life Science, Hokkaido University , N21, W11, Kita-ku, Sapporo 001-0021, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yokoi
authors.affiliation: Graduate School of Life Science and Faculty of Advanced Life Science, Hokkaido University , N21, W11, Kita-ku, Sapporo 001-0021, Japan.|Medicinal Chemistry Pharmaceuticals, Co., Ltd. , N21, W12, Kita-ku, Sapporo 001-0022, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hinou
authors.affiliation: Graduate School of Life Science and Faculty of Advanced Life Science, Hokkaido University , N21, W11, Kita-ku, Sapporo 001-0021, Japan.|Medicinal Chemistry Pharmaceuticals, Co., Ltd. , N21, W12, Kita-ku, Sapporo 001-0022, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Nishimura
mesh_terms: D020816:Amino Acid Motifs; D015415:Biomarkers / Q000097:blood; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry; D006020:Glycopeptides / Q000138:chemical synthesis / Q000737:chemistry; D006031:Glycosylation; D017563:Lung Diseases, Interstitial / Q000097:blood*; D018396:Mucin-1 / Q000097:blood* / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques
chemical_list: D015415:Biomarkers; D006020:Glycopeptides; D018396:Mucin-1