# Beta-peptide

β-peptides consist of β amino acids, which have their amino group bonded to the β carbon rather than the α carbon as in the 20 standard biological amino acids. The only common naturally occurring β amino acid is β-alanine; although it is used as a component of larger bioactive molecules, β-peptides in general do not appear in nature. For this reason β-peptide-based antibiotics are being explored as ways of evading antibiotic resistance. Early studies in this field were published in 1996 by the group of Dieter Seebach[1] and that of Samuel Gellman.[2]

## Chemical structure and synthesis

In α amino acids (molecule at left), both the carboxylic acid group (red) and the amino group (blue) are bonded to the same carbon center, termed the α carbon ($\mathrm{C}^{\alpha}$) because it is one atom away from the carboxylate group. In β amino acids, the amino group is bonded to the β carbon ($\mathrm{C}^{\beta}$), which is found in most of the 20 standard amino acids. Only glycine lacks a β carbon, which means that β-glycine is not possible.

The chemical synthesis of β amino acids can be challenging, especially given the diversity of functional groups bonded to the β carbon and the necessity of maintaining chirality. In the alanine molecule shown, the β 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 β amino acids and their derivatives[3][4] notably those based on the Arndt-Eistert synthesis.

Two main types of β-peptides exist: those with the organic residue (R) next to the amine are called β3-peptides and those with position next to the carbonyl group are called β2-peptides.[5]

## Secondary structure

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

Many types of helix structures consisting of β-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, β-peptides form a more stable helix than α-peptides.[6]

## Clinical potential

β-peptides are stable against proteolytic degradation in vitro and in vivo, an important advantage over natural peptides in the preparation of peptide-based drugs.[7] β-Peptides have been used to mimic natural peptide-based antibiotics such as magainins, which are highly potent but difficult to use as drugs because they are degraded by proteolytic enzymes in the body.[8]