Efficient preparation of selenopeptides to ease fatigue
Selenopeptides could one day be used to treat fatigue, but the first step is discovering how to best synthesize the supplement
image: Solid-phase peptide synthesis via 9-fluorenylmethoxycarbonyl strategy enables stepwise C-to-N assembly of selenopeptides on resin through repeated coupling, deprotection, and washing cycles, followed by cleavage. Nitrogen prevents selenium oxidation; vacuum filtration accelerates washing. The selenohydryl group of selenocysteine requires methoxybenzyl protection, whereas selenomethionine does not.
Credit: Food Science of Animal Products, Tsinghua University Press
Fatigue is physical and mental exhaustion that can often be an early sign of severe health conditions. Current treatments for fatigue are mostly behavioral, including light physical activity, improved diet, stress reduction, and rest. Researchers are studying additional ways to manage fatigue, including supplements and enriched foods.
A recent review of available research points to selenopeptides as a possible anti-fatigue intervention. The review was published in Food Science of Animal Products on 12 December, 2025.
“With the continuous improvement of living standards, public health awareness has been steadily increasing. Selenopeptides, owing to their unique molecular structure and significant antioxidant activity, have demonstrated considerable application potential in anti-fatigue interventions, particularly within functional foods and dietary supplements,” said Wei Jia, a professor at the School of Food Science and Engineering at Shaanxi University of Science and Technology in Ankang, China.
Selenium is an essential trace element, and selenium deficiency has been linked to diseases and cardiovascular disorders. In some patients with fatigue, immune cells called autoantibodies have been shown to erroneously target selenium transport proteins, keeping the selenium from getting to its destination and reducing selenoprotein expression. This suggests that selenium may play a role in preventing and reducing fatigue.
The review analyzed the different ways selenopeptides are prepared. Selenopeptides can be extracted from selenium-enriched animal and plant proteins and microbial proteins or synthesized. While conventional techniques like enzymatic hydrolysis, microbial fermentation, and selenium modification all have their benefits, they also have significant drawbacks. Focusing on chemical synthesis of selenopeptides with distinct stricture and exceptionally high purity is essential for testing this supplement in clinical trials.
The review looked at solid-phase peptide synthesis and liquid-phase peptide synthesis as a way of engineering selenopeptides. Solid-phase peptide synthesis is most often used during the discovery phase of supplement development, but at an industrial scale it can be an inefficient process that produces substantial waste. However, novel approaches are improving solid-phase peptide synthesis by reducing waste and improving product purity. “Solid-phase peptide synthesis, as the cornerstone of selenopeptide chemistry, is achieved through the deep integration of green chemistry and process engineering, breaking free from the dual shackles of toxicity and waste, and ushering in a new era of efficient, precise, and sustainable peptide synthesis,” said Jia.
Because of some of the challenges associated with solid-phase peptide synthesis, researchers are studying alternatives such as liquid-phase peptide synthesis. This method reduces purification steps and uses less solvent, making the process of developing selenopeptides easier to scale and more environmentally friendly. “Liquid-phase peptide synthesis is an important development direction in peptide preparation. It not only provides new ideas for the synthesis of complex structured and modified peptides but also offers a feasible path for green pharmaceutical processes,” said Jia.
Looking ahead, researchers are looking toward testing selenopeptides as an anti-fatigue intervention and better understanding its benefits and risks. “Further research should focus on constructing well-characterized selenopeptide libraries through chemical synthesis, systematically evaluation structure-activity relationships, pharmacokinetic profiles, and long-term safety, as well as elucidating the underlying mechanisms of action in vivo,” said Jia.
Other contributors include Yuxiao Guo, Rong Zhang, Fen Ao, and Haizhen Mo of Shaanxi University and Bo He of Ankang Research and Development Center for Se-enriched Products.
The National Key Research and Development Program of China and Key Laboratory of Se-enriched Products Development and Quality of Control, Ministry of Agriculture and Rural Affairs/National-Local Joint Engineering Laboratory of Se-enriched Food Development supported this research.
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