title: Chemical Approach to a Whole Body Imaging of Sialo-N-Linked Glycans.
abstract: PET and noninvasive fluorescence imaging of the sialo-N-linked glycan derivatives are described. To establish the efficient labeling protocol for N-glycans and/or glycoconjugates, new labeling probes of fluorescence and ⁶⁸Ga-DOTA, as the positron emission nucleus for PET, through rapid 6π-azaelectrocyclization were designed and synthesized, (E)-ester aldehydes. The high reactivity of these probes enabled the labeling of lysine residues in peptides, proteins, and even amino groups on the cell surfaces at very low concentrations of the target molecules (~10⁻⁸ M) within a short reaction time (~5 min) to result in "selective" and "non-destructive" labeling of the more accessible amines. The first MicroPET of glycoproteins, ⁶⁸Ga-DOTA-orosomucoid and asialoorosomucoid, successfully visualized the differences in the circulatory residence of glycoproteins, in the presence or absence of sialic acids. In vivo dynamics of the new N-glycoclusters, prepared by the "self-activating" Huisgen cycloaddition reaction, could also be affected significantly by their partial structures at the non-reducing end, i.e., the presence or absence of sialic acids, and/or sialoside linkages to galactose. Azaelectrocyclization chemistry is also applicable to the engineering of the proteins and/or the cell surfaces by the oligosaccharides; lymphocytes chemically engineered by sialo-N-glycan successfully target the tumor implanted in BALB/C nude mice, detected by noninvasive fluorescence imaging.
authors.affiliation: Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043, Japan, ktzenori@chem.sci.osaka-u.ac.jp.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Tanaka
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukase
mesh_terms: D000818:Animals; D001212:Asialoglycoproteins / Q000737:chemistry* / Q000378:metabolism; D002465:Cell Movement; D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000378:metabolism; D008214:Lymphocytes / Q000737:chemistry / Q000166:cytology; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism; D009961:Orosomucoid / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D012794:Sialic Acids / Q000737:chemistry* / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods; D051598:Whole Body Imaging / Q000379:methods*
chemical_list: D001212:Asialoglycoproteins; D006571:Heterocyclic Compounds; D009844:Oligosaccharides; D009942:Organometallic Compounds; D009961:Orosomucoid; D012794:Sialic Acids; C017030:asialoorosomucoid; C016735:sialooligosaccharides; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D008239:Lysine