Analytical Tools

Concomitant with the advances in transcriptomics, proteomics and glycomics has been a growth in the research technology that supports the basic scientific inquiries. New synthetic technologies provide significantly improved access to glycoconjugates, which are complex carbohydrates that are covalently linked with other chemical species. Advanced methods of polymerization and use of solution and/or solid-phase synthesis facilitate the preparation of branched carbohydrates and hybrids of carbohydrates conjugated to polymers.

The ability to create appropriate research material is critical for mapping the molecular structure-function relationship at interfaces between carbohydrates and proteins. One of the primary roadblocks in the development of glycomics has been analysis of glycan structures, which are generally available only in small quantities from natural sources. Synthesis of these complex compounds is essential to advances in both glycomics and proteomics. Commercial enterprises that succeed in developing analytical tools not only for research but also the resulting applications of the research will be poised at the forefront of the emerging biotechnologies.

Glycomics research emerges from proteomics research. Current successful proteomic methods reflect the convergence of the latest mass spectrometry technologies, protein chemistry and separation sciences, plus advances in genomics and bioinformatics. Yet, no proteomic platform available today is suitable for all areas of research. However, proteomics remains a viable option for improved biomarkers, diagnostics and treatment of disease. Meanwhile the advances in analytical tools for proteomics over the last decade, particularly in mass spectrometry (MS) methods, are applicable to sensitive and definitive glycan analysis.

The state of the art in MS applications for glycomics utilizes both electrospray and matrix assisted laser desorption/ionization – time of flight (MALDI-TOF) mass spectrometry. MALDI-TOF has become a tool of choice for large molecule analyses and facilitates rapid profiling of complex cell or tissue glycomes to be profiled and identification of important minor structures. Glycoproteomics approaches based on these tools can be used to define the variant glycans located at specific attachment sites within glycoproteins. Analyzing the different glycoforms is an important aspect of proteomics because glycoforms can significantly alter protein function and underscores the interrelationship of the fields of study.
In fact, in 2008, researchers at the University of California, Davis who were studying ovarian cancer cells reported on a study that utilized matrix-assisted laser desorption ionization (MALDI) Fourier transformation mass spectrometry (FTMS) techniques. MALDI-FTMS was able to identify unique glycan markers which may be biomarkers for diagnosis of ovarian cancer (1). This preliminary study suggests that glycomics profiling of tissue samples may be useful for the detection of ovarian cancer.

The latest technological advancement applicable to glycomics is the development of glycoarrays which can also be called carbohydrate microarrays. Glycoarrays involve tens or even hundreds of different sugars that are bonded covalently or bound noncovalently in small areas on a solid surface. These arrays of glycans can be utilized to screen cell extracts or libraries of biological compounds to assess the carbohydrate-binding properties of the sample. Applications for glycoarrays include basic research into glycomics, drug discovery, and diagnosis. Glycoarrays can be used to map carbohydrate and protein partners in highly specific interactions of the glycome. Glycoarrays have already been used, for example, to study a receptor on leukocytes linked to immunity to fungal pathogens.

The ability to produce glycan structures is an important tool for research in glycomics, spawning yet another related field called chemical glycomics. Chemical glycomics provides the potential glycoengineering, the creation of non-natural glycan-based structures. These technologies have already produced anthrax and malaria vaccine candidates.

The complexities of the data generated from glycomics research require the parallel development of appropriate bioinformatics platforms to integrate the diverse datasets produced by the different technologies already discussed above. The goal of these bioinformatics applications is to create a systems biology approach to glycan structure-function relationships. Also needed are various modeling software and related glycoinformatics to study the molecular dynamics of glycans and proteins. Databases capable of expressing the three-dimensional structures bioactive glycans are also necessary. There is also a need for unique relational glycoinformatic databases since the information is not suitable for storage in database structures developed for DNA and proteins. New software packages are required, as well as platforms that allow data sharing. A Glycan Data Exchange (GLYDE) standardized data format is being developed as well as an international network of distributed databases for the glycosciences based at the European Bioinformatics Institute.

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