Other Unnatural Amino Acids


Unnatural amino acids are amino acids that are not encoded by any of the 64 existing genetic codons. The site-specificity, low perturbation of protein structure, high sensitivity and flexibility of use of non-natural amino acid systems have led to their application in basic research and drug discovery, bioengineering and other fields. Unnatural amino acids are also widely used to detect changes in protein structure, drug conjugation, and biosensors.


A range of non-natural amino acids have been used for protein modification in bacteria, yeast and mammalian cells with great precision and efficiency; most of them are derivatives of 20 natural amino acids, and the unnatural amino acids derivatives reported today are phenylalanine derivatives, tyrosine derivatives, glutamine derivatives, alanine derivatives, leucine derivatives, serine derivatives, lysine derivatives, etc.


Non-natural amino acids are major components of synthetic peptides and peptide-like drugs, both domestically and internationally, and have a significant role in biochemistry, medicine, and the food sector, etc.

1. Applications in Biocatalysis

By introducing unnatural structural components such as unnatural amino acids into proteins, artificial enzymes with high catalytic activity or completely new reactivity can be obtained, with the expectation of achieving unnatural chemical reactions that are comparable to the catalytic efficiency of natural enzymes and extending the application of biocatalysis in organic synthesis. In addition, non-natural amino acid technology has been successfully applied to the establishment of a light-energy fixed CO2 enzyme, enabling artificial photosynthesis.

2. Applications in Pharmacy

Many of the drugs currently on the market contain structures of unnatural amino acids. The most important angiotensin-converting enzyme (ACE) inhibitors for the treatment of hypertension mostly contain side chain structures of unnatural amino acids. l-norvaline is the main intermediate in the synthesis of perindopril, a third-generation angiotensin-converting enzyme inhibitor. Antitumour and antiviral drugs synthesized from non-natural amino acids are less toxic and more selective in humans, and many varieties have shown good efficacy and promise. For example, leucine derivatives are key side chains in the synthesis of the antiviral drug atazanavir, an antiretroviral drug used to treat human immunodeficiency virus (HIV) infection. D-Alanine has been used extensively in the synthesis of intermediates for Alzheimer's drugs. Peptide analgesics consisting of unnatural amino acids do not have the gastrointestinal side effects of clinically used analgesics and are long-lasting and effective. For example, hyoscine, which is synthesized using a phenylalanine derivative, is now in clinical use.

3. Applications in Food Industry

In addition, unnatural amino acids have a role in the food sector, as dipeptides or short peptides (aspartame) made up of D-amino acids are sweet, safe, non-caloric and suitable for consumption by the general population as well as by obese and diabetic patients.

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