:2-Aminoisobutyric acid
{{Chembox
| Watchedfields = changed
| verifiedrevid = 477197928
| Name = 2-Aminoisobutyric acid
| ImageFile = 2-aminoisobutyric acid.svg
| ImageSize = 170
| ImageFile1 = 2-Methylalanine-3D-balls.png
| ImageSize1 = 180
| ImageAlt1 = 2-methylalanine molecule
| PIN = 2-Amino-2-methylpropanoic acid
| OtherNames = α-Aminoisobutyric acid
2-Methylalanine
|Section1={{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5891
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C03665
| InChI = 1/C4H9NO2/c1-4(2,5)3(6)7/h5H2,1-2H3,(H,6,7)
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 27971
| SMILES = O=C(O)C(N)(C)C
| InChIKey = FUOOLUPWFVMBKG-UHFFFAOYAD
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C4H9NO2/c1-4(2,5)3(6)7/h5H2,1-2H3,(H,6,7)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = FUOOLUPWFVMBKG-UHFFFAOYSA-N
| CASNo = 62-57-7
| CASNo_Ref = {{cascite|correct|CAS}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 1E7ZW41IQU
| EC_number = 200-544-0
| PubChem = 6119
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB02952
}}
|Section2={{Chembox Properties
| C=4 | H=9 | N=1 | O=2
| MolarMass = 103.12 g/mol
| Appearance = white crystalline powder
| Solubility = soluble
| Density = 1.09 g/mL
| BoilingPtC = 204.4
| pKa= {{ubl
| 2.36 (carboxyl; H2O)
| 10.21 (amino; H2O){{cite book | editor= Haynes, William M. | year = 2016 | title = CRC Handbook of Chemistry and Physics | edition = 97th | publisher = CRC Press | isbn = 978-1498754286 | page=5–88 | title-link = CRC Handbook of Chemistry and Physics }}
}}
}}
}}
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,{{cite news |title=Immune System of Humans, Other Mammals Could Struggle to Fight Extraterrestrial Microorganisms |url=http://www.sci-news.com/space/mammalian-immune-system-extraterrestrial-microorganisms-08668.html |newspaper=Science News |date=23 July 2020 |access-date=24 July 2020 }} 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.{{OrgSynth | last1 = Clarke | first1 = H. T. | last2 = Bean | first2 = H. J. | title = α-Aminoisobutyric acid | prep = cv2p0029 | year = 1931 | volume = 11 | pages = 4 | collvol = 2 | collvolpages = 29}}.
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.{{Cite journal|last1=Toniolo|first1=C.|last2=Crisma|first2=M.|last3=Formaggio|first3=F.|last4=Peggion|first4=C.|date=2001|title=Control of peptide conformation by the Thorpe-Ingold effect (C alpha-tetrasubstitution)|url=https://pubmed.ncbi.nlm.nih.gov/12209474|journal=Biopolymers|volume=60|issue=6|pages=396–419|doi=10.1002/1097-0282(2001)60:6<396::AID-BIP10184>3.0.CO;2-7|issn=0006-3525|pmid=12209474}} Oligomers of AIB form 310 helices.
Ribosomal incorporation into peptides
{{see also|Cell-free system|Cell-free protein synthesis}}
2-Aminoisobutyric acid is compatible with ribosomal elongation of peptide synthesis. Katoh et al. used flexizymes{{Cite journal|last1=Ohuchi|first1=Masaki|last2=Murakami|first2=Hiroshi|last3=Suga|first3=Hiroaki|title=The flexizyme system: a highly flexible tRNA aminoacylation tool for the translation apparatus|journal=Current Opinion in Chemical Biology|volume=11|issue=5|pages=537–542|doi=10.1016/j.cbpa.2007.08.011|pmid=17884697|year=2007}} and an engineered a tRNA body to enhance the affinity of aminoacylated AIB-tRNA species to elongation factor P.{{Cite journal|last1=Katoh|first1=Takayuki|last2=Iwane|first2=Yoshihiko|last3=Suga|first3=Hiroaki|date=2017-12-15|title=Logical engineering of D-arm and T-stem of tRNA that enhances d-amino acid incorporation|journal=Nucleic Acids Research|language=en|volume=45|issue=22|pages=12601–12610|doi=10.1093/nar/gkx1129|pmid=29155943|issn=0305-1048|pmc=5728406}} 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.{{Cite journal|last1=Iqbal|first1=Emil S.|last2=Dods|first2=Kara K.|last3=Hartman|first3=Matthew C. T.|title=Ribosomal incorporation of backbone modified amino acids via an editing-deficient aminoacyl-tRNA synthetase|journal=Organic & Biomolecular Chemistry|volume=16|issue=7|pages=1073–1078|language=en|doi=10.1039/c7ob02931d|pmid=29367962|pmc=5993425|issn=1477-0539|year=2018}}