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Agilent Inks Collaboration with Gachon University for Glycoprotein Biomarker Research

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Agilent this week announced a collaboration with South Korea's Gachon University of Medicine and Science for the discovery of protein and glycoprotein biomarkers in diabetes and cancer.

Under the collaboration, Agilent will provide Gachon researchers, led by professor Hookeun Lee, with early access to separations, mass spec, and bioinformatics technology to advance their glycoproteomic analyses. Lee is currently investigating glycoproteins as markers for colon and gastric cancer and plans in the near future to explore markers for cardiac disease caused by diabetes.

In an e-mail to ProteoMonitor, Rudi Grimm, Agilent's collaboration manager for South Asia Pacific and Korea, said the agreement would revolve primarily around use and development of Agilent's HPLC chips for glycan analyses and the development of "a glycan database that consists of accurate mass, retention time, and MS/MS spectra of glycans."

He noted that the agreement would focus mainly on providing Gachon researchers with "early technology access" but that Agilent would also as part of the deal sponsor several PhD students at the university. The collaboration is expected to last "at least for three years," Grimm said, "and, if successful, for many more years to come."

Glycoproteomics is a significant area of focus for biomarker research, with glycosylated proteins comprising roughly 80 percent of the protein biomarkers currently in clinical use. These modifications have been linked to wide variety of diseases, including cancer, rheumatoid arthritis, and diabetes.

"A lot of biology happens at the level of glycans and not at the protein level," Grimm said.

However, glycoproteomics has proven challenging due to the lability of these modifications as well as their great complexity and diversity. Unlike other protein post-translational modifications like phosphorylation or acetylation, glycosylations consist of complex, branching sugar structures, making them difficult to analyze and catalogue via mass spec.

As Pauline Rudd, professor of glycobiology at University College, Dublin, and also an Agilent collaborator (PM 7/9/2010), told ProteoMonitor in a 2010 interview, "a sugar ring has six carbons and those carbons can all link to other carbons in monosaccharides. So you get these complex branched structures, which means you can't just do straightforward mass spec to get the composition because that's not going to tell you which monosaccharides and how those monosaccharides are linked together."

Key to improved glycoproteomic analyses "is a separation module that can separate complex glycan mixtures," Grimm said, adding that Agilent's HPLC glycan chip "is capable of separating every single stereoisomer of glycans that exist." He also noted that "development of further HPLC chips for the separation of various glycan classes" will be a primary aim of the Gachon collaboration.

In its collaboration with Rudd, Agilent is working on the development of a two-dimensional HPLC chip for glycan analysis. The Gachon collaboration, on the other hand, will focus "more on N- and O-linked glycan biomarkers using special 1D chips," Rudd said.

It will also explore a gold nanoparticle-based workflow for enriching N-glycosylated peptides recently developed by Lee and his colleagues that Grimm called "another very interesting aspect of our collaboration."

Detailed in a paper published last year in Analyst, the researchers' technique uses hydrazide-functionalized gold nanoparticles to capture glycosylated peptides in biological samples for analysis. Using an Agilent HPLC chip and Q-TOF mass spec, Lee and his team determined that these particles captured glycopeptides with greater than 90 percent specificity, demonstrating, they wrote, that they are suitable for high-throughput analysis of glycoproteins.

The announcement marks Agilent's second glycomics collaboration in recent years with a South Korean institution. Last year, the firm signed a deal with Korea's Chungnam National University to develop new applications and tools for glycan analysis (GWDN 8/23/2011). That collaboration is being led by Grimm and Chungnam researcher Hyun Joo An. Under it, the university is developing glycomics training course for Agilent customers and employees and serving as a strategic glycomics reference site for the company.

Agilent isn't alone is pursuing glycomics collaborations in the region. Chungnam and An also have a deal with Bruker to develop MALDI-TOF-based methodologies for glycan analysis (GWDN 12/2/2012).

Bruker also recently released its GlycoQuest glycan search engine software for mass spec-based glycomics and glycoproteomics research. Other mass spec vendors have likewise staked out a presence in the glycomics space – several of them, including Waters and Thermo Fisher Scientific, through co-marketing deals with informatics firm Premier Biosoft for that company's SimGlycan glycomics software.

In addition to the Gachon glycoproteomics collaboration, Agilent also announced this week an agreement with Seoul's Samsung Medical Center to use Agilent instruments for clinical research, including protein biomarker work.

The parties said that the center's Department of Laboratory Medicine & Genetics Research will use Agilent's 6530 Q-TOF and 6430 triple quadrupole mass specs. According to a statement by Sung-Hwa Hong, the center's executive vice president of research and development, the collaboration will include work on "the discovery and validation of protein biomarkers for applications in clinical trials… and assay development for a tumor marker for certain cancers and diseases."

In addition, researchers from both Samsung Medical Center and Agilent plan to work on joint research projects that "evaluate novel and powerful analytical technologies for future uses in clinical environments," Grimm said in a statement.