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 commonly 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 and that of Samuel Gellman.
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 () because it is one atom away from the carboxylate group. In β amino acids, the amino group is bonded to the β carbon (), 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 atom. A number of synthesis mechanisms have been introduced to efficiently form β amino acids and their derivatives 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.
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.
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. 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.
See also 
- Seebach D, Overhand M, Kühnle FNM, Martinoni B, Oberer L, Hommel U, Widmer H (June 1996). "β-Peptides: Synthesis by Arndt-Eistert homologation with concomitant peptide coupling. Structure determination by NMR and CD spectroscopy and by X-ray crystallography. Helical secondary structure of a -hexapeptide in solution and its stability towards pepsin". Helvetica Chimica Acta 79 (4): 913–941. doi:10.1002/hlca.19960790402.
- Appella DH, Christianson LA, Karle IL, Powell DR, Gellman SH (1996). "β-Peptide Foldamers: Robust Helix Formation in a New Family of -Amino Acid Oligomers". J. Am. Chem. Soc. 118 (51): 13071–2. doi:10.1021/ja963290l.
- Basler B, Schuster O, Bach T (November 2005). "Conformationally constrained β-amino acid derivatives by intramolecular [2 + 2]-photocycloaddition of a tetronic acid amide and subsequent lactone ring opening". J. Org. Chem. 70 (24): 9798–808. doi:10.1021/jo0515226. PMID 16292808.
- Murray JK, Farooqi B, Sadowsky JD, et al. (September 2005). "Efficient synthesis of a β-peptide combinatorial library with microwave irradiation". J. Am. Chem. Soc. 127 (38): 13271–80. doi:10.1021/ja052733v. PMID 16173757.
- Seebach D, Matthews JL (1997). "β-Peptides: a surprise at every turn". Chem. Commun. (21): 2015–22. doi:10.1039/a704933a.
- Gademann K, Hintermann T, Schreiber JV (October 1999). "Beta-peptides: twisting and turning". Curr. Med. Chem. 6 (10): 905–25. PMID 10519905.
- Beke T, Somlai C, Perczel A (January 2006). "Toward a rational design of β-peptide structures". J Comput Chem 27 (1): 20–38. doi:10.1002/jcc.20299. PMID 16247761.
- Porter EA, Weisblum B, Gellman SH (2002). "Mimicry of host-defense peptides by unnatural oligomers: antimicrobial β-peptides". J. Am. Chem. Soc. 124 (25): 7324–30. doi:10.1021/ja0260871. PMID 12071741.