{"id":2861,"date":"2010-11-30T21:36:32","date_gmt":"2010-11-30T19:36:32","guid":{"rendered":"http:\/\/localhost\/azgad\/wordpress\/?p=2861"},"modified":"2010-11-30T21:36:32","modified_gmt":"2010-11-30T19:36:32","slug":"large-tree-like-sugar-clusters-provide-potential-in-vivo-probes-for-cancer-cells","status":"publish","type":"post","link":"https:\/\/azgad.com\/?p=2861","title":{"rendered":"Large tree-like sugar clusters provide potential in vivo probes for cancer cells"},"content":{"rendered":"

.
\nChallenges in isolating and synthesizing protein-bound sugar molecules
\ncalled N-glycans, which help stabilize insulin levels and modulate
\n antibody-dependent immune responses among many other important
\nprocesses in the body, has limited the investigation of their function and
\ninteraction with cultured cells and dissected tissues. Now, a team led by
\nYasuyoshi Watanabe and Satoshi Nozaki from the RIKEN Center for
\nMolecular Imaging Science (CMIS), Kobe, has developed the first series
\nof fluorescent and radioactive probes to track these molecules in living
\nanimals, which may eventually be used to track tumors.
\n.
\n.
\n\"\"<\/a>.
\n.
\nFigure 1: The structure of the tree-like cluster with 16 sugar branches
\n.
\nAccording to Nozaki, N-glycans, which contain sialic acid residues, always
\nform clusters in vivo allowing them to maximize their interactions and selectivity
\ntowards N-glycan-binding proteins and other biomolecules. \u201cIt is rather rare that
\n a single molecule of N-glycan shows significant biological activity,\u201d he says.
\n.
\nTo recreate these in vivo conditions, the researchers worked in close collaboration with
\nKatsunori Tanaka from Osaka University to attach up to 16 sugar molecules to branched
\nlysine oligopeptides, creating the largest tree-like oligosaccharide cluster ever prepared
\n (Fig. 1). After linking the clusters to fluorescent and radioactive labels, they injected the
\n resulting probes into the tail vein of immunodeficient mice.
\n.
\nPositron emission tomography (PET) imaging showed that the number of glycans in the
\nclusters determined their lifetime in vivo. Four- and eight-sugar clusters rapidly disappeared
\n through the kidney in just one hour. Clusters containing 16 N-glycans, however, remained
\n in the body for over four hours before being eliminated through the kidney and the gallbladder
\n\u2014a desirable feature when studying how N-glycans travel in living subjects.
\n.
\nFurthermore, the team discovered that differences in the way the sialic acids are connected to the
\nN-glycans influenced cluster behavior and build up in specific organs. The so-called (2\u20136)-linked
\nsialic acids stabilized the clusters in serum, leading to their accumulation in the liver through
\n interactions with specific protein receptors. In contrast, their (2\u20133)-linked congeners rapidly cleared
\n through the bladder. Also, fluorescence imaging revealed that clusters bearing both types of linkages
\n were most fluorescent in the spleen, suggesting their capture by a part of the immune system
\ncalled the reticuloendothelial system.
\n.
\nThe researchers hope to use these clusters as molecular probes for tumors. They are also planning
\n to prepare clusters consisting of three to four different glycans in order to enhance the selectivity of
\nthe probes toward tumors and specific organs. \u201cNobody has done it, but the data shows that we can
\n achieve it,\u201d says Nozaki.<\/p>\n","protected":false},"excerpt":{"rendered":"

. Challenges in isolating and synthesizing protein-bound sugar molecules called N-glycans, which help stabilize insulin levels and modulate antibody-dependent immune responses among many other important processes in the body, has limited the investigation of their function and interaction with cultured cells and dissected tissues. Now, a team led by Yasuyoshi Watanabe and Satoshi Nozaki from … <\/p>\n

\u05d4\u05de\u05e9\u05d9\u05db\u05d5 \u05d1\u05e7\u05e8\u05d9\u05d0\u05d4<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[10],"tags":[330,154,513,186],"class_list":["post-2861","post","type-post","status-publish","format-standard","hentry","category-10","tag-330","tag-154","tag-513","tag-186","nodate","item-wrap"],"_links":{"self":[{"href":"https:\/\/azgad.com\/index.php?rest_route=\/wp\/v2\/posts\/2861","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/azgad.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/azgad.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/azgad.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/azgad.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=2861"}],"version-history":[{"count":1,"href":"https:\/\/azgad.com\/index.php?rest_route=\/wp\/v2\/posts\/2861\/revisions"}],"predecessor-version":[{"id":2863,"href":"https:\/\/azgad.com\/index.php?rest_route=\/wp\/v2\/posts\/2861\/revisions\/2863"}],"wp:attachment":[{"href":"https:\/\/azgad.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2861"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/azgad.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2861"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/azgad.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2861"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}