2-Aminoisobutyric acid


2-Aminoisobutyric acid, or α-aminoisobutyric acid or α-methylalanine or 2-methylalanine, is the non-proteinogenic amino acid with the structural formula H2N-C2-COOH. It is rare in nature only being found in meteorites, 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.
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. It is a strong helix inducer in peptides. Oligomers of AIB form 310 helices.
3-Aminoisobutyric acid, or BAIBA, is found as a normal metabolite of skeletal muscle in 2014. The plasma concentrations are increased in human by exercise. The production is likely a result of enhanced mitochondrial activity as the increase is also observed in the muscle of PGC-1a overexpression mice. BAIBA is proposed as protective factor against metabolic disorder since it can induce brown fat function.

Ribosomal incorporation into peptides

Several reports have confirmed the compatibility of 2-aminoisobutyric acid with ribosomal elongation of peptide synthesis. Katoh et al. used flexizymes and an engineered a tRNA body to enhance the affinity of aminoacylated AIB-tRNA species to elongation factor-P. 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.