2-Aminoisobutyric acid, or α-aminoisobutyric acid (AIB) or α-methylalanine or 2-methylalanine, is an amino acid with the structural formula is H2N-C(CH3)2-COOH. It is contained in some antibiotics of fungal origin, e.g. alamethicin and some lantibiotics. It is not one of the proteinogenic amino acids and is rather rare in nature (cf. non-proteinogenic amino acids).
1 Synthesis 2 Biological activity 3 Ribosomal incorporation into peptides 4 References
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 (cf. non-proteinogenic amino acids). It is a strong helix inducer in peptides. Oligomers of AIB form 310 helices. BAIBA, or 3-aminoisobutyric acid, 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. References
^ Dawson, R.M.C., et al., Data for Biochemical Research, Oxford, Clarendon Press, 1959. ^ Clarke, H. T.; Bean, H. J. (1931). "α-Aminoisobutyric acid". Organic Syntheses. 11: 4. ; Collective Volume, 2, p. 29 . ^ Roberts Lee D, Boström P, O Sullivan John F, Schinzel Robert T, Lewis Gregory D, Dejam A, Lee Y-K, Palma Melinda J, Calhoun S, Georgiadi A, Chen M-H, Ramachandran Vasan S, Larson Martin G, Bouchard C, Rankinen T, Souza Amanda L, Clish Clary B, Wang Thomas J, Estall Jennifer L, Soukas Alexander A, Cowan Chad A, Spiegelman Bruce M, Gerszten Robert E. "β-Aminoisobutyric acid induces browning of white fat and hepatic β-oxidation and is inversely correlated with cardiometabolic risk factors". Cell Metabolism 2014;19:96–108. CS1 maint: Uses authors parameter (link) ^ 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. doi:10.1016/j.cbpa.2007.08.011. ^ 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. 45 (22): 12601–12610. doi:10.1093/nar/gkx1129. ISSN 0305-1048. ^ 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. doi:10.1039/c7ob02931d. ISSN