title: Visualizing Trimming Dependence of Biodistribution and Kinetics with Homo- and Heterogeneous N-Glycoclusters on Fluorescent Albumin.
abstract: A series of N-glycans, each sequentially trimmed from biantennary sialoglycans, were homo- or heterogeneously clustered efficiently on fluorescent albumin using a method that combined strain-promoted alkyne-azide cyclization and 6π-azaelectrocyclization. Noninvasive in vivo kinetics and dissection analysis revealed, for the first time, a glycan-dependent shift from urinary to gall bladder excretion mediated by sequential trimming of non-reducing end sialic acids. N-glycoalbumins that were trimmed further, in particular, GlcNAc- and hybrid biantennary-terminated congeners, were selectively taken up by sinusoidal endothelial and stellate cells in the liver, which are critical for diagnosis and treatment of liver fibrillation. Our glycocluster strategy can not only reveal the previously unexplored extracellular functions of N-glycan trimming, but will be classified as the newly emerging glycoprobes for diagnostic and therapeutic applications.
authors.affiliation: Biofunctional Synthetic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ogura
authors.affiliation: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tahara
authors.affiliation: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nozaki
authors.affiliation: Osaka Women's Junior College, 3-8-1 Kasugaoka, Fujiidera-shi, Osaka, 583-8558, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Morimoto
authors.affiliation: Disease Glycomics Team, Global Research Cluster, RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kizuka
authors.affiliation: Disease Glycomics Team, Global Research Cluster, RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kitazume
authors.affiliation: Micro-Signaling Regulation Technology Unit, RIKEN Center for Life Science Technologies, Wako-shi, Saitama, 351-0198, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Hara
authors.affiliation: Micro-Signaling Regulation Technology Unit, RIKEN Center for Life Science Technologies, Wako-shi, Saitama, 351-0198, Japan.
authors.forename: Soichi
authors.initials: S
authors.lastname: Kojima
authors.affiliation: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Onoe
authors.affiliation: Biofunctional Chemistry Laboratory, A. Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya Street, Kazan 420008, Russia.
authors.forename: Almira
authors.initials: A
authors.lastname: Kurbangalieva
authors.affiliation: Disease Glycomics Team, Global Research Cluster, RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
authors.affiliation: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Biofunctional Synthetic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.|Biofunctional Chemistry Laboratory, A. Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya Street, Kazan 420008, Russia.|Japan Science and Technology Agency-PRESTO, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D001692:Biological Transport; D002240:Carbohydrate Sequence; D005456:Fluorescent Dyes / Q000737:chemistry; D005690:Galactose / Q000737:chemistry* / Q000378:metabolism; D005704:Gallbladder / Q000378:metabolism; D006031:Glycosylation; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D066237:Intestinal Elimination / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D061848:Optical Imaging; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D065667:Renal Elimination / Q000502:physiology; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D012794:Sialic Acids / Q000737:chemistry* / Q000378:metabolism; D012795:Sialoglycoproteins / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D013194:Staining and Labeling; D001743:Urinary Bladder / Q000378:metabolism
chemical_list: D005456:Fluorescent Dyes; D011134:Polysaccharides; D012709:Serum Albumin; D012794:Sialic Acids; D012795:Sialoglycoproteins; D005690:Galactose