Beta-peptide

&beta;-peptides consist of &beta; amino acids, which have their amino group bonded to the &beta; carbon rather than the &alpha; carbon as in the 20 standard biological amino acids. The only commonly naturally occurring &beta; amino acid is &beta;-alanine; although it is used as a component of larger bioactive molecules, &beta;-peptides in general do not appear in nature. For this reason &beta;-peptide-based antibiotics are being explored as ways of evading antibiotic resistance.

Chemical structure and synthesis
In &alpha; amino acids (molecule at left in Figure 1), both the carboxylic acid group (red) and the amino group (blue) are bonded to the same carbon, termed the &alpha; carbon ($$\mathrm{C}^{\alpha}$$) because it is one atom away from the carboxylate group. In &beta; amino acids, the amino group is bonded to the &beta; carbon ($$\mathrm{C}^{\beta}$$), which is found in most of the 20 standard amino acids. Only glycine lacks a &beta; carbon, which means that there is no &beta;-glycine molecule.

The chemical synthesis of &beta; amino acids can be challenging, especially given the diversity of functional groups bonded to the &beta; carbon and the necessity of maintaining chirality. In the alanine molecule shown, the &beta; carbon is achiral; however, most larger amino acids have a chiral $$\mathrm{C}^{\beta}$$ atom. A number of synthesis mechanisms have been introduced to efficiently form &beta; amino acids and their derivatives.

Secondary Structure
Because the backbones of &beta;-peptides are longer than those of peptides that consist of &alpha;-amino acids, &beta;-peptides form different secondary structures. The alkyl substituents at both the &alpha; and &beta; positions in a &beta; amino acid favor a gauche conformation about the bond between the &alpha;-carbon and &beta;-carbon. This also affects the thermodynamic stability of the structure.

Many types of helix structures consisting of &beta;-peptides have been reported. These conformation types are distinguished by the number of atoms in the hydrogen-bonded ring that is formed in solution; 8-helix, 10-helix, 12-helix, 14-helix, and 10/12-helix have been reported. Generally speaking, &beta;-peptides form a more stable helix than &alpha;-peptides.

Clinical potential
&beta;-peptides are stable against proteolytic degradation in vitro and in vivo, an important advantage over natural peptides in the preparation of peptide-based drugs. &beta;-peptides have been used to mimic natural peptide-based antibiotics such as magainins, which are extremely powerful but difficult to use as drugs because they are degraded by proteolytic enzymes in the body.