2-Aminoisobutyric acid (Aib) is the non-proteinogenic amino acid with the structural formula H<sub>2</sub>N-C(CH<sub>3</sub>)<sub>2</sub>-COOH. The Aib residue is a component of tirzepatide, a commonly prescribed antidiabetic medication for treatment of type 2 diabetes. Although uncommon, it is also found in some natural products
2-Aminoisobutyric acid can be prepared from acetone cyanohydrin, by reaction with ammonia followed by hydrolysis.
The compound is not chiral, unlike most amino acids. It is a strong helix inducer in peptides due to ThorpeâÂÂIngold effect of its gem-dimethyl group. Oligomers of Aib form 3<sub>10</sub> helices.
2-Aminoisobutyric acid is not one of the proteinogenic amino acids and is rather rare in nature (cf. non-proteinogenic amino acids). In the context of cell-free protein synthesis 2-aminoisobutyric acid is compatible with ribosomal elongation of peptide synthesis. Flexizymes and an engineered tRNA body 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 valineâÂÂtRNA ligase to synthesize aminoacylated Aib-tRNA<sup>Val</sup>. The aminoacylated tRNA was subsequently used in a cell-free translation system to yield Aib-containing peptides.
Aib has been found in meteorites and some antibiotics of fungal origin, such as alamethicin and some lantibiotics.