Dipeptide

Examples

Commercial value

About six dipeptides are of commercial interest.

• Aspartame (N-L-α-aspartyl-L-phenylalanine 1-methyl ester) is an artificial sweetener.
• Carnosine (beta-alanyl-L-histidine) and Anserine (beta-alanyl-N-methyl histidine) are highly concentrated in muscle and brain tissues. They are used in sports medicines.
• Acetylcarnosine, cataract prevention
• Ala-Gln and Gly-Tyr, infusion
• Val-Tyr, antihypertensive

Other dipeptides

• Homoanserine (N-(4-aminobutyryl)-L-histidine) is another dipeptide identified in the brain and muscles of mammals.
• Kyotorphin (L-tyrosyl-L-arginine) is a neuroactive dipeptide which plays a role in pain regulation in the brain.
• (or ophidine) (beta-alanyl-N tau-methyl histidine) has been identified in the muscles of several species of mammal (including man), and the chicken.
• Glorin (N-propionyl-γ-L-glutamyl-L-ornithine-δ-lac ethyl ester) is a chemotactic dipeptide for the slime mold Polysphondylium violaceum.
• Barettin (cyclo-[(6-bromo-8-en-tryptophan)-arginine]) is a cyclic dipeptide from the marine sponge Geodia barretti.
• Dialanine is commonly used as a model in molecular dynamics.
• Xenortides, isolated from the bacterium Xenorhabdus nematophila

Production

Synthetic dipeptides

Dipeptides are produced by coupling amino acids. The amino group on one amino acid is rendered non-nucleophilic (P in eq) and the carboxylic acid group in the second amino acid is deactivated as its methyl ester. The two modified amino acids are then combined in the presence of a coupling agent, which facilitates formation of the amide bond: :RCH(NHP)CO2H + R'CH(NH2)CO2CH3 → RCH(NHP)C(O)NH(CHR')CO2CH3 + H2O Subsequent to this coupling reaction, the amine protecting group P and the ester are converted to the free amine and carboxylic acid, respectively.

For many amino acids, the ancillary functional groups are protected. The condensation of the amine and the carboxylic acid to form the peptide bond generally employs coupling agents to activate the carboxylic acid.

The Bergmann azlactone peptide synthesis is a classic organic synthesis for the preparation of dipeptides.

Biosynthesis

Dipeptides are produced from polypeptides by the action of the hydrolase enzyme dipeptidyl peptidase. Dietary proteins are digested to dipeptides and amino acids, and the dipeptides are absorbed more rapidly than the amino acids, because their uptake involves a separate mechanism. Dipeptides activate G-cells found in the stomach to secrete gastrin.

Diketopiperazines (cyclic dipeptides)

References

References

1. (November 2008). "Synthesis and application of dipeptides; current status and perspectives". Applied Microbiology and Biotechnology.
2. (1997). "Glutamine dipeptides in clinical nutrition". Nutrition.
3. (2013). "Low-epimerization Peptide Bond Formation with Oxyma Pure: Preparation of Z-L-Phg-Val-OMe". Organic Syntheses.
4. (2015). "Dipeptide Syntheses via Activated α-Aminoesters". Organic Syntheses.
5. "Hydrolysis of a dipeptide".
6. (January 2013). "Methods and Principles in Medicinal Chemistry: Protein-Protein Interactions in Drug Discovery". Wiley-VCH.
7. (July 2012). "2,5-Diketopiperazines: synthesis, reactions, medicinal chemistry, and bioactive natural products". Chemical Reviews.