Isotope-labeled Carbohydrates

Introduction

Carbohydrates, where they are synonym of saccharide, are found throughout nature. Carbohydrates are polyhydroxy aldehydes and ketones that form essential structural elements in nature, confer individuality to biological surfaces, and are vital intermediates in the production and storage of energy in biological systems. When one or more atoms of carbohydrates are replaced by the stable isotopes of that atom, that is stable isotope-labeled carbohydrates. Carbohydrates contain multiple carbon, hydrogen, and oxygen atoms, and sometimes nitrogen atoms, making possible a wide range of different isotopomers of any given carbohydrates that include ¹³C, ²H, ¹⁸O, and ¹⁵N stable isotopes. Carbohydrates can be singly (site-selective), multiply, or uniformly labeled in a given isotope. More than one type of isotope can be present in a labeled carbohydrate ^[1].

Synthesis

Take the synthesis method of stable isotope-labeled monosaccharides as example. Because monosaccharides are the smallest carbohydrates and the basic molecular units of various carbohydrates like disaccharides and polysaccharides.

Chemical and enzymic methods are often considered for the preparation of monosaccharide isotopomers that are singly and multiply labeled with ¹³C, ²H, ¹⁸O, and ¹⁵N isotopes. The attractiveness of enzymic approaches lies in their normally high yields and specificity in comparison to chemical methods. However, the enzyme-catalyzed reactions are not always superior to chemical method. There are, and will continue to be, efficient chemical reactions that are easy to perform on large scales and give excellent yields. Two primary isotope insertion reactions in chemical method are cyanohydrin reduction (CR) and molybdate-catalyzed epimerization (MCE). Thus, optimal synthetic protocols for the synthesis of simple stable isotope-labeled monosaccharides and their assembly into oligomers (for example, oligosaccharides, oligonucleotides) will frequently be composed of integrated chemical and enzymic reactions.

Fig. 1 The scheme of use of cyanohydrin reduction to introduce carbon, hydrogen, and oxygen isotopes into aldoses.

Applications

Carbohydrates play important roles in many key biochemical processes in living cells. For example, they are metabolized to produce energy, mediate cell-cell recognition, and play an indirect role (as constituents of DNA and RNA) in DNA replication, RNA transcription, and protein synthesis. These roles, and others of comparable biochemical significance, have been studied by the use of stable isotope-labeled carbohydrates, usually in conjunction with NMR spectroscopy and/or mass spectrometry ^[2]. For examples, carbohydrate metabolism of glucose kinetics in whole-body has been monitored with the use of isotopically labeled glucose and [6,6-²H] glucose has generally been the tracer of choice in such studies. Molecular aspects of cell-cell recognition, mediated by cell-surface glycoproteins and glycolipids, have been probed through NMR studies of stable isotope-labeled oligosaccharides. ¹³C-labeled carbohydrates have been used in a small number of carbohydrate-protein interaction studies ^[3].

Fig. 2 The schematic diagram of carbohydrate-protein interaction studies by using ¹³C-labeled carbohydrate.

In addition, stable isotope-labeled carbohydrates can also be used in the other aspect studies. For example, the carbohydrate composition in algal biomass was analyzed using fully ¹³C labeled sugars as internal standards in gas chromatography/mass spectrometry (GC/MS), which is considered as a convenient, reliable, and accurate single-platform workflow and offers advantages over existing methods ^[4]. Solution compositions of simple reducing sugars and rates of anomerization, oligosaccharide conformation also have been studied by stable isotope-labeled carbohydrates.

Fig. 3 The schematic diagram of analysis of carbohydrate composition in algal biomass by using fully ¹³C labeled sugars.

What can we offer?

As a professional supplier of stable isotope-labeled compounds, Alfa Chemistry has always shown great interest in the latest developments in stable isotope-labeled carbohydrates. Alfa Chemistry has excellent R&D staffs with rich experience who aim to provide high quality and cost-effective stable isotope-labeled carbohydrates timely. We can offer you with various stable isotope-labeled carbohydrates such as monosaccharides, disaccharides, polysaccharides with labeled with ¹³C, ²H, ¹⁸O, and ¹⁵N isotopes. You can click on our product list for a detailed view. If you do not find the product you want, we also provide you with custom synthesis service. Please contact us, if you are in need of assistance.

References

• Zhang, W., et al. Labeling monosaccharides with stable isotopes[M]. Methods in Enzymology, Academic Press, 2015, 565: 423-458.
• Serianni, A. S. Stable-isotope-labeled carbohydrates and nucleosides: synthesis and applications in chemistry and biology[R]. Los Alamos National Lab. (LANL), Los Alamos, NM (United States), 1994.
• Nestor, G., et al. Exploiting uniformly ¹³C-labeled carbohydrates for probing carbohydrate–protein interactions by NMR spectroscopy[J]. Journal of the American Chemical Society, 2017, 139(17): 6210-6216.
• McConnell, B. O. and Antoniewicz, M. R. Measuring the composition and stable-isotope labeling of algal biomass carbohydrates via gas chromatography/mass spectrometry[J]. Analytical chemistry, 2016, 88(9): 4624-4628.