2-Aminoisobutyric acid explained

2-Aminoisobutyric acid (also known as α-aminoisobutyric acid, AIB, α-methylalanine, or 2-methylalanine) is the non-proteinogenic amino acid with the structural formula H2N-C(CH3)2-COOH. It is rare in nature, having been only found in meteorites,[1] and some antibiotics of fungal origin, such as alamethicin and some lantibiotics.

Synthesis

In the laboratory, 2-aminoisobutyric acid may be prepared from acetone cyanohydrin, by reaction with ammonia followed by hydrolysis.[2] Industrial scale synthesis can be achieved by the selective hydroamination of methacrylic acid.

Biological activity

2-Aminoisobutyric acid is not one of the proteinogenic amino acids and is rather rare in nature (cf. non-proteinogenic amino acids). It is a strong helix inducer in peptides due to Thorpe–Ingold effect of its gem-dimethyl group.[3] Oligomers of AIB form 310 helices.

Ribosomal incorporation into peptides

See also: Cell-free system and Cell-free protein synthesis.

2-Aminoisobutyric acid is compatible with ribosomal elongation of peptide synthesis. Katoh et al. used flexizymes[4] and an engineered a tRNA body to enhance the affinity of aminoacylated AIB-tRNA species to elongation factor P.[5] The result was an increased incorporation of AIB into peptides in a cell free translation system. Iqbal et al.. used an alternative approach of creating an editing deficient valine—tRNA ligase to synthesize aminoacylated AIB-tRNAVal. The aminoacylated tRNA was subsequently used in a cell-free translation system to yield AIB-containing peptides.[6]

References

  1. News: Immune System of Humans, Other Mammals Could Struggle to Fight Extraterrestrial Microorganisms . Science News . 23 July 2020 . 24 July 2020 .
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  3. Toniolo. C.. Crisma. M.. Formaggio. F.. Peggion. C.. 2001. Control of peptide conformation by the Thorpe-Ingold effect (C alpha-tetrasubstitution). Biopolymers. 60. 6. 396–419. 10.1002/1097-0282(2001)60:6<396::AID-BIP10184>3.0.CO;2-7. 0006-3525. 12209474.
  4. Ohuchi. Masaki. Murakami. Hiroshi. Suga. Hiroaki. The flexizyme system: a highly flexible tRNA aminoacylation tool for the translation apparatus. Current Opinion in Chemical Biology. 11. 5. 537–542. 10.1016/j.cbpa.2007.08.011. 17884697. 2007.
  5. Katoh. Takayuki. Iwane. Yoshihiko. Suga. Hiroaki. 2017-12-15. Logical engineering of D-arm and T-stem of tRNA that enhances d-amino acid incorporation. Nucleic Acids Research. en. 45. 22. 12601–12610. 10.1093/nar/gkx1129. 29155943. 0305-1048. 5728406.
  6. Iqbal. Emil S.. Dods. Kara K.. Hartman. Matthew C. T.. Ribosomal incorporation of backbone modified amino acids via an editing-deficient aminoacyl-tRNA synthetase. Organic & Biomolecular Chemistry. 16. 7. 1073–1078. en. 10.1039/c7ob02931d. 29367962. 5993425. 1477-0539. 2018.