A-amino isobutyric acid

The peptaibol antibiotics are a group of linear oligopeptides (of 15 to 24 residues) characterised by the presence of a high content of a-amino isobutyric acid (Aib) residues and an amino alcohol group at the C-terminus. These substances are frequently obtained as a complex mixture of closely related compounds. For example... 

An interesting extension of this has led to the synthesis of a-amino-isobutyric acid (Aib), in which one of the prochiral methyl groups, the Pro-(f )-methyl, has been labeled with deuterium (85LA1917). In this synthesis the R group in structure (193) was CD3 derived from CD3I. 

For further information on C -disubstituted glycines, see also Section 10.3. a-Amino-isobutyric acid (Aib, 1) (Scheme 2), also known as C -methylalanine, is the prototype of the class of residues termed C -disubstituted glycines. It is also the nonproteinogenic a-amino acid with the highest helix propensity. Aib has two methyl groups on the a-carbon. The extra methyl group severely limits the possible 4> and i) values, such that allowed regions of... 

If the a hydrogen is substituted as, for example, in a-amino isobutyric acid (Aib), then the conformational energy (< >,t j) map is very restricted, and the preferred form of Aib peptides is computed to be the 310 rather than the a-helical form.150 This prediction has been verified by NMR and infrared spectroscopic measurements on solutions of oligomers of Aib.151 The stability of the 310-helix for short poly(Aib-L-alanine) polypeptides and the increased stabilization of the a-helical form with a lengthening of the chain have been demonstrated recently.152... 

Figure 1. Typical HPLC chromatograms of the OPA-NAC (II) derivitized amino acids detected from the spark discharge reactions. Chromatograms labeled with roman numerals I.) Amino acid standard, II.) CO2/N2 not sparked, III.) CO2/N2 + CaCOs, sparked, hydrolyzed- ascorbate. IV.) CO2/N2, sparked, hydrolyzed - ascorbate V.) CO2/N2, sparked + CaCOs, hydrolyzed + ascorbate. Amino acids I.) DL aspartic acid 2.) DL glutamic acid 3.) DL serine 4.) glycine 5.) P-alanine 6.) DL alanine 7.) a-amino isobutyric acid 8.) DL norleucine (internal standard). The D and L enantiomers of glutamic acid and serine are not separated under these chromatographic conditions.

Remarkably, nearly half of the amino acid components are L-a-amino-isobutyric acid residues (Aib), an amino acid not present in ribosome-manufactured proteins (p. 8). Peptides containing Aib-residues have been recognized to form a-helices particularly readily, an explanation of the pore forming properties of alamethicins and of similar natural and artificial polypeptides. In the natural analogs alanine or valine is found to be replaced by Aib closely related natural compounds are among others, suzukacillin, trichotoxin (mould products), and less similar, a component of bee venom, the 25-peptide mellitin. In the synthesis of peptides containing a-amino-isobutyric acid certain difficulties are encountered due to the poor steric accessibility of the amino—as well as of the carboxyl group. 

NMR-spectra of a- and y-L-glutamyl-a-amino-isobutyric acid and some related... 

Oxazolinones are five-membered azlactones (in some older publications referred to as oxazolones) that can be obtained from a-amino acids, for example, from a-amino isobutyric acid, and carboxylic acids (Scheme 9). 

Alanine-lactic acid, /-alanine-a-hydroxyisobutyric acid and a-amino-isobutyric acid-lactic block copolymers were prepared by copolymerization of the respective a-amino acid A-carboxy anhydride and a-hydroxy-acid-anhydrosulfite in benzene in the presence of triethylamine. Specific cleavage of the ester bonds by hydroxylamine in the cold confirmed the AB block structure of short chain lengths. 

Using ab initio calculations of the model dipeptide CH3-CONH-CH2-CONH-CH3, the VCD of the four most common secondary structures of proteins were calculated and compared successfully with experimental spectra of albumin, concanavalin A, (Aib)2Leu(Aib)5 and poly(L-lysine) (with Aib = a-amino isobutyric acid). The main structure of these proteins is the a-helical, -sheet, poly(L-proline)II conformation. 

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