{"605861":{"#nid":"605861","#data":{"type":"news","title":"Chemical Octopus Catches Sneaky Cancer Clues, Trace Glycoproteins","body":[{"value":"\u003Cp\u003ECancer drops sparse chemical hints of its presence early on, but\u0026nbsp;unfortunately, many of them are in a class of biochemicals that could not\u0026nbsp;be detected thoroughly, until now.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EResearchers at the Georgia Institute of Technology have \u003Ca href=\u0022https:\/\/www.nature.com\/articles\/s41467-018-04081-3\u0022 target=\u0022_blank\u0022\u003Eengineered a chemical trap\u003C\/a\u003E that exhaustively catches what are called glycoproteins, including minuscule traces that have previously escaped detection.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGlycoproteins are protein molecules bonded with sugar molecules, and they\u0026rsquo;re very common in all living things. Glycoproteins come in myriad varieties and sizes and make up important cell structures like cell receptors. They also wander around our bodies in secretions like \u003Ca href=\u0022https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/2701489\u0022 target=\u0022_blank\u0022\u003Emucus\u003C\/a\u003E or\u0026nbsp;\u003Ca href=\u0022https:\/\/www.hormone.org\/hormones-and-health\/hormones\/hormones-and-what-do-they-do\u0022 target=\u0022_blank\u0022\u003Ehormones\u003C\/a\u003E.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EBut some glycoproteins are very, very rare\u0026nbsp;and\u0026nbsp;can serve as an early signal, or \u003Ca href=\u0022https:\/\/www.cancer.gov\/publications\/dictionaries\/cancer-terms\/def\/biomarker\u0022 target=\u0022_blank\u0022\u003Ebiomarker\u003C\/a\u003E, indicating there\u0026rsquo;s something wrong in the body \u0026ndash; like cancer. Existing methods to reel in glycoproteins for laboratory examination are relatively new and have had big holes in their nets, so many of these molecules, especially those very rare ones\u0026nbsp;produced by cancer, have tended to slip by.\u003C\/p\u003E\r\n\r\n\u003Ch4\u003E\u003Cstrong\u003ECancerous traces\u003C\/strong\u003E\u003C\/h4\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;These tiny traces are critically important for early disease detection,\u0026rdquo; said principal investigator Ronghu Wu, \u003Ca href=\u0022http:\/\/petitinstitute.gatech.edu\/ronghu-wu\u0022 target=\u0022_blank\u0022\u003Ea professor in Georgia Tech\u0026rsquo;s School of Chemistry and Biochemistry\u003C\/a\u003E. \u0026ldquo;When cancer is just getting started, aberrant glycoproteins are produced and secreted into body fluids such as blood and urine. Often their abundances are extremely low, but catching them is urgent.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThis new chemical trap, which took Georgia Tech \u003Ca href=\u0022https:\/\/www.nature.com\/articles\/s41467-018-04081-3\u0022 target=\u0022_blank\u0022\u003Echemists several years to develop\u003C\/a\u003E and is based on a \u003Ca href=\u0022https:\/\/en.wikipedia.org\/wiki\/Boronic_acid\u0022 target=\u0022_blank\u0022\u003Eboronic acid\u003C\/a\u003E, has proven extremely effective in lab tests including on cultured human cells and mouse tissue samples.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;This method is very universal,\u0026rdquo; said first author Haopeng Xiao, a graduate research assistant. \u0026ldquo;We get over 1,000 glycoproteins in a really small lab sample.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EIn comparison tests with existing methods, the chemical trap, a complex molecular construction reminiscent of an octopus, captured exponentially more glycoproteins, especially more of those trace glycoproteins.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EWu, Xiao and Weixuan Chen, a former Georgia Tech postdoctoral researcher, who was also first author of the study alongside Xiao, \u003Ca href=\u0022https:\/\/www.nature.com\/articles\/s41467-018-04081-3\u0022 target=\u0022_blank\u0022\u003Epublished their results in the journal \u003Cem\u003ENature Communications\u003C\/em\u003E.\u003C\/a\u003E The research was funded by the National Science Foundation and the National Institutes of Health.\u003C\/p\u003E\r\n\r\n\u003Ch4\u003E\u003Cstrong\u003EBoronic bungles\u003C\/strong\u003E\u003C\/h4\u003E\r\n\r\n\u003Cp\u003EFor chemistry whizzes, here\u0026rsquo;s a short summary of \u003Ca href=\u0022http:\/\/www.nature.com\/articles\/s41467-018-04081-3\u0022 target=\u0022_blank\u0022\u003Ehow the researchers made the octopus\u003C\/a\u003E. They took a good thing and doubled then tripled down on it.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThose who recall high school chemistry class may still know what boric acid is, as do people who use it to kill roaches. Its chemical structure is an atom of boron bonded with three hydroxyl groups (H\u003Csub\u003E3\u003C\/sub\u003EBO\u003Csub\u003E3\u003C\/sub\u003E).\u003C\/p\u003E\r\n\r\n\u003Cp\u003EBoronic acids are a family of organic compounds that build on boric acid. There are many members of the \u003Ca href=\u0022https:\/\/en.wikipedia.org\/wiki\/Boronic_acid\u0022 target=\u0022_blank\u0022\u003Eboronic acid\u003C\/a\u003E family, and they tend to bond well with glycoproteins, but their bonds can be less reliable than needed.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;Most boronic acids let too many low-abundance glycoproteins get away,\u0026rdquo; Wu said. \u0026ldquo;They can catch glycoproteins that are in high abundance but not those in low abundance, the ones that tell us more valuable things about cell development or about human disease.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Ch4\u003E\u003Cstrong\u003EBenzoboroxole octopus\u003C\/strong\u003E\u003C\/h4\u003E\r\n\r\n\u003Cp\u003EBut the Georgia Tech chemists were able to leverage the strengths of\u0026nbsp;boronic acids to develop a glycoprotein capturing method that works exceptionally well.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EFirst, they tested several boronic acid derivatives and found that one called \u003Ca href=\u0022http:\/\/www.chemspider.com\/Chemical-Structure.13570654.html\u0022 target=\u0022_blank\u0022\u003Ebenzoboroxole\u003C\/a\u003E strongly bound with each sugar component on the glycopeptide. (\u0026ldquo;\u003Ca href=\u0022https:\/\/en.wikipedia.org\/wiki\/Peptide\u0022 target=\u0022_blank\u0022\u003EPeptide\u003C\/a\u003E\u0026rdquo; refers to the basic chemical composition of a protein.) \u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThen they stitched many benzoboroxole molecules together with other components to form a \u0026quot;\u003Ca href=\u0022https:\/\/www.google.com\/search?q=dendrimer\u0026amp;oq=dendrimer\u0026amp;aqs=chrome..69i57j0l5.462j0j4\u0026amp;sourceid=chrome\u0026amp;ie=UTF-8\u0022 target=\u0022_blank\u0022\u003Edendrimer,\u0026quot; which refers to the resulting\u0026nbsp;branch- or tentacle-like structure\u003C\/a\u003E. The finished large molecule resembled an octopus ready to go after those sugar components.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EIn its middle, similarly positioned to an octopus\u0026#39;s head, was a magnetic bead, which acted as a kind of handle. Once the dendrimer caught a glycoprotein, the researchers used a magnet to grab the bead and pull out their chemical octopus along with its ensnared glycopeptides (e.g. glycoproteins).\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;Then we washed the dendrimer off with a low pH solution, and we had the glycoproteins analyzed with things like mass spectrometry,\u0026rdquo; Wu said.\u003C\/p\u003E\r\n\r\n\u003Ch4\u003E\u003Cstrong\u003ECancer treatments?\u003C\/strong\u003E\u003C\/h4\u003E\r\n\r\n\u003Cp\u003EThe researchers have some ideas about how medical laboratory researchers could make practical use of the new Georgia Tech method to detect odd biomolecules emitted by cancer, such as \u003Ca href=\u0022https:\/\/www.britannica.com\/science\/antigen\u0022 target=\u0022_blank\u0022\u003Eantigens\u003C\/a\u003E. For example, the chemical octopus could improve detection of \u003Ca href=\u0022https:\/\/www.cancer.gov\/types\/prostate\/psa-fact-sheet\u0022 target=\u0022_blank\u0022\u003Eprostate-specific antigens (PSA)\u003C\/a\u003E in prostate cancer screenings.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;PSA is a glycoprotein. Right now, if the level is very high, we know that the patient may have cancer, and if it\u0026rsquo;s very low, we know cancer is not likely,\u0026rdquo; Wu said. \u0026ldquo;But there is a gray area in between, and this method could lead to much more detailed information in that gray area.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThe researchers also believe that developers could leverage the chemical invention to produce targeted cancer treatments. Immune cells could be trained to recognize the aberrant glycoproteins, track down their source cancer cells in the body and kill them.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThe research\u0026rsquo;s potential for science goes far beyond its possible future medical applications.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThe fields of \u003Ca href=\u0022https:\/\/www.genome.gov\/18016863\/a-brief-guide-to-genomics\/\u0022 target=\u0022_blank\u0022\u003Egenomics\u003C\/a\u003E and \u003Ca href=\u0022https:\/\/www.sciencedirect.com\/topics\/neuroscience\/proteomics\u0022 target=\u0022_blank\u0022\u003Eproteomics\u003C\/a\u003E have made great strides. Following in their footsteps, this new molecular trap could advance the study of the rising field of \u003Ca href=\u0022https:\/\/commonfund.nih.gov\/glycoscience\u0022 target=\u0022_blank\u0022\u003Eglycoscience\u003C\/a\u003E.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E------\u003C\/p\u003E\r\n\r\n\u003Cp\u003ELike this article?\u0026nbsp;\u003Ca href=\u0022http:\/\/www.rh.gatech.edu\/subscribe\u0022 target=\u0022_blank\u0022\u003EGet our email newsletter here.\u003C\/a\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EALSO read: \u003Ca href=\u0022http:\/\/www.rh.gatech.edu\/news\/605259\/remote-control-shoots-laser-nano-gold-turn-cancer-killing-immune-cells\u0022 target=\u0022_blank\u0022\u003ECancer-killing T-cells switched on via remote control\u003C\/a\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cem\u003EGeorgia Tech\u0026rsquo;s Johanna Smeekens coauthored the research paper. The research was funded by the National Science Foundation (CAREER award CHE-1454501), and the National Institutes of Health (R01GM118803). Findings and any opinions are those of the authors\u0026rsquo; and not necessarily of the funding agencies.\u003C\/em\u003E\u003C\/p\u003E\r\n","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003ECertain minuscule cancer signals easily evade detection, but perhaps no longer. Biomarkers made of glycoproteins are bound to get snared in the tentacles of this chemical octopus that Georgia Tech chemists devised over several years. The monstrous molecule could also be a windfall for the rising field of glycoscience.\u003C\/p\u003E\r\n","format":"limited_html"}],"field_summary_sentence":[{"value":"Tiny cancer signals of the glycoprotein sort evade detection, but they\u0027ll have a hard time dodging the new \u0022chemical octopus.\u0022"}],"uid":"31759","created_gmt":"2018-05-04 17:15:01","changed_gmt":"2018-05-09 14:08:54","author":"Ben Brumfield","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2018-05-04T00:00:00-04:00","iso_date":"2018-05-04T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"594424":{"id":"594424","type":"image","title":"iStock cancer cells illustration","body":null,"created":"1502800506","gmt_created":"2017-08-15 12:35:06","changed":"1525450970","gmt_changed":"2018-05-04 16:22:50","alt":"","file":{"fid":"226552","name":"cancer clipped 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