Alamethicin 3-alanine

Two model peptides—alamethicin which is a-helix peptaibol-transmembrane antimicrobial peptide (AMP) and synthetic a-helix alanine-rich peptide (K3A18K3)—inserted into l,2-dimyristoyl-sn-glycero-3-phosphatidylcholine... 

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. 

It is known that the helical conformation of alamethicin would provide a channel too small to allow passage of ions, since it has been calculated that the interior of an a-helix of poly-L-alanine has an energy barrier of approximately 840 kJ mol for passage of protons The alamethicin pores arise from circular a regates of jKirallel... 

Microorganisms and plants can synthesize many uncommon amino acids. For example, some microbes make 2-aminoisobutyric acid and lanthionine, which is a sulfide-bridged derivative of alanine. Both of these amino acids are found in peptidic lantibiotics such as alamethicin. While in plants, 1-aminocyclopropane-l-carboxylic acid is a small disubstituted cyclic amino acid that is a key intermediate in the production of the plant hormone ethylene. 

---