2-Aminoisobutyric acid

2-Aminoisobutyric acid
2-methylalanine molecule
Names
Preferred IUPAC name
2-Amino-2-methylpropanoic acid
Other names
α-Aminoisobutyric acid
2-Methylalanine
α-methylalanine
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
DrugBank
ECHA InfoCard 100.000.495 Edit this at Wikidata
EC Number
  • 200-544-0
KEGG
UNII
  • InChI=1S/C4H9NO2/c1-4(2,5)3(6)7/h5H2,1-2H3,(H,6,7) checkY
    Key: FUOOLUPWFVMBKG-UHFFFAOYSA-N checkY
  • InChI=1/C4H9NO2/c1-4(2,5)3(6)7/h5H2,1-2H3,(H,6,7)
    Key: FUOOLUPWFVMBKG-UHFFFAOYAD
  • O=C(O)C(N)(C)C
Properties
C4H9NO2
Molar mass 103.12 g/mol
Appearance white crystalline powder
Density 1.09 g/mL
Boiling point 204.4 °C (399.9 °F; 477.5 K)
soluble
Acidity (pKa)
  • 2.36 (carboxyl; H2O)
  • 10.21 (amino; H2O)[1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

2-Aminoisobutyric acid (Aib) is the non-proteinogenic amino acid with the structural formula H2N-C(CH3)2-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][3]

Synthesis and structure

2-Aminoisobutyric acid can be prepared from acetone cyanohydrin, by reaction with ammonia followed by hydrolysis.[4]

The compound is not chiral, unlike most amino acids. It is a strong helix inducer in peptides due to Thorpe–Ingold effect of its gem-dimethyl group.[5][3] Oligomers of Aib form 310 helices.

Biological activity

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[6] and an engineered tRNA body enhance the affinity of aminoacylated Aib-tRNA species to elongation factor P.[7] 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.[8]

Other occurrences

Aib has been found in meteorites[9] and some antibiotics of fungal origin, such as alamethicin and some lantibiotics.

References

  1. ^ Haynes, William M., ed. (2016). CRC Handbook of Chemistry and Physics (97th ed.). CRC Press. p. 5–88. ISBN 978-1498754286.
  2. ^ Das, Manoj K.; Raghothama, S.; Balaram, P. (1986). "Membrane channel forming polypeptides. Molecular conformation and mitochondrial uncoupling activity of antiamoebin, an .alpha.-aminoisobutyric acid containing peptide". Biochemistry. 25 (22): 7110–7117. doi:10.1021/bi00370a053. PMID 2432929.
  3. ^ a b Misra, Rajkumar; Rudnick-Glick, Safra; Adler-Abramovich, Lihi (2021). "From Folding to Assembly: Functional Supramolecular Architectures of Peptides Comprised of Non-Canonical Amino Acids". Macromolecular Bioscience. 21 (8) 2100090. doi:10.1002/mabi.202100090. PMID 34142442.
  4. ^ Clarke, H. T.; Bean, H. J. (1931). "α-Aminoisobutyric acid". Organic Syntheses. 11: 4. doi:10.15227/orgsyn.011.0004..
  5. ^ 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. doi:10.1002/1097-0282(2001)60:6<396::AID-BIP10184>3.0.CO;2-7. ISSN 0006-3525. PMID 12209474.
  6. ^ Ohuchi, Masaki; Murakami, Hiroshi; Suga, Hiroaki (2007). "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. PMID 17884697.
  7. ^ 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. PMC 5728406. PMID 29155943.
  8. ^ Iqbal, Emil S.; Dods, Kara K.; Hartman, Matthew C. T. (2018). "Ribosomal incorporation of backbone modified amino acids via an editing-deficient aminoacyl-tRNA synthetase". Organic & Biomolecular Chemistry. 16 (7): 1073–1078. doi:10.1039/c7ob02931d. ISSN 1477-0539. PMC 5993425. PMID 29367962.
  9. ^ "Immune System of Humans, Other Mammals Could Struggle to Fight Extraterrestrial Microorganisms". Science News. 23 July 2020. Retrieved 24 July 2020.
allikas: https://en.wikipedia.org/wiki/2-aminoisobutyric_acid