Stable Isotope Labeling of Natural Products

BOC Sciences provides stable isotope labeling services. We manufacture stable isotope labeled natural products and use them as tracers and internal standards in a wide range of life science research areas and diagnostics.

Fig.1 An isotopic labeling approach linking natural products. (McCaughey et al., 2022)

Why Isotope Labeling of Natural Products?

Isotope labeling can be used to study the synthetic pathways and biosynthetic mechanisms of natural products. By providing a labeled compound as a precursor to an organism or culture medium, the origin and transformation pathways of specific atoms in the product can be determined. This helps to reveal the synthetic pathways, enzyme-catalyzed reactions and metabolic regulatory mechanisms of natural products. Isotope labeling can also help identify the biologically active sites of natural products. By introducing isotopic labeling into the molecular structure, it is possible to identify specific atoms or functional groups that play a key role in the biological activity of a natural product. This is important for drug design and optimization.

Stable Isotope Labeling for Natural Products

Natural products can be isotopically labeled by a variety of methods, depending on the structure of the target compound and the desired labeling position.

(1) Chemical synthesis labeling

Isotopes are introduced into target compounds by using isotope labeling reagents during chemical synthesis. For example, compounds with stable isotopes can be used as reaction substrates or reagents, thereby introducing isotopic labeling into specific positions of the target molecule.

(2) Biosynthetic labeling

For biosynthetic pathways of natural products, labeling can be achieved by providing isotope-labeled substrates in the organism or cell culture medium.

(3) Metabolic labeling

Metabolic labeling involves providing isotopically labeled compounds to an organism that introduces the isotope into a natural product through its metabolic process. By tracking the isotopic labeling of metabolites, metabolic pathways and reaction mechanisms can be studied.

(4) Enzyme-catalyzed labeling

Certain enzymes can catalyze isotope-labeling reactions, thereby introducing isotopes into target compounds. By selecting the appropriate enzyme and substrate, labeling of a specific functional group or position can be achieved.

Available Isotope Labeling Reagents

• ²H-labeled glucose, alcohols.
• ¹³C-labeled glucose, acetic acid, propionic acid.
• ¹⁵N-labeled amino acids, urea.
• ¹⁸O-labeled water, phenolic acid.

The types of labeling reagents we can provide are not limited to the above, but can be customized according to customer needs.

Types of Stable Isotope Labeled Natural Products

• Alkaloids: Alkaloids can be labeled using stable isotope labeled nitrogen sources, common methods include using nitrogen isotope labeled urea or other nitrogen containing compounds.
• Polysaccharides: Polysaccharides, glycans, etc. can be labeled using stable isotope labeled monosaccharides or other carbon sources. Carbon isotope-labeled glucose or other monosaccharides may be used as precursors.
• Steroids: Steroids are a class of natural products that contain a tetracyclic carbon skeleton. For steroids, carbon isotope-labeled alcohols or ketones can be used as precursors.
• Phenols: Phenolic compounds bear hydroxyl groups and can be labeled with oxygen isotope-labeled water or other oxygen sources.
• Acids: Acids bear carboxyl groups and can be labeled using carbon isotope-labeled ketones or alcohols as precursors.

Advantages

• Analytical HPLC and MS are performed in every development cycle
• Full spectrum of modification and stable isotope labeling services
• Multiple stable isotope labeling methods
• Rich natural product compound library

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