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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. Pioneering studies in this field were published in 1996 by the group of Dieter Seebach [1] and that of Gellman [2].

Additional recommended knowledge


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, termed the α carbon (Cα) because it is one atom away from the carboxylate group. In β amino acids, the amino group is bonded to the β carbon (Cβ), which is found in most of the 20 standard amino acids. Only glycine lacks a β carbon, which means that there is no β-glycine molecule.

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 Cβ 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].

The β-peptide zwit-1F with a fully described quaternary structure [7] is called a β-protein because it has many characteristics of an actual protein. Eight 12-helix units self-assemble in water to a superstructure with a hydrophobic inner core.

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 [8]. β-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 [9].


  1. ^ 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 Volume 79, Issue 4, Date: 26 Juni 1996, Pages: 913-941 Dieter Seebach, Mark Overhand, Florian N. M. Kühnle, Bruno Martinoni, Lukas Oberer, Ulrich Hommel, Hans Widmer doi:10.1002/hlca.19960790402
  2. ^ β-Peptide Foldamers: Robust Helix Formation in a New Family of -Amino Acid Oligomers Appella, D. H.; Christianson, L. A.; Karle, I. L.; Powell, D. R.; Gellman, S. H. J. Am. Chem. Soc.; (Communication); 1996; 118(51); 13071-13072. doi:10.1021/ja963290l
  3. ^ Basler B, Schuster O, Bach T. (2005). Conformationally constrained beta-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. 2005 doi:10.1021/jo0515226 [1].
  4. ^ Murray JK, Farooqi B, Sadowsky JD, Scalf M, Freund WA, Smith LM, Chen J, Gellman SH. (2005). Efficient synthesis of a beta-peptide combinatorial library with microwave irradiation. J. Am. Chem. Soc. 127(38):13271-80. 2005 doi:10.1021/ja052733v[2]
  5. ^ β-Peptides: a surprise at every turn Dieter Seebach and Jennifer L. Matthews Chem. Commun., 1997, (21),2015-2022 doi:10.1039/a704933a
  6. ^ Gademann K, Hintermann T, Schreiber JV. (1999). "Beta-peptides: twisting and turning.", Curr Med Chem Oct;6(10):905-25. [3].
  7. ^ High-Resolution Structure of a β-Peptide Bundle Daniels, D.S., Petersson, E.J., Qiu, J.X., and Schepartz, A. J. Am. Chem. Soc., 129, 6, 1532 - 1533, 2007, doi:10.1021/ja068678n
  8. ^ Beke T, Somlai C, Perczel A. (2006). "Toward a rational design of beta-peptide structures.", J Comp Chem Jan 15;27(1):20-38. [4].
  9. ^ Porter EA, Weisblum B, Gellman SH. (2002). Mimicry of host-defense peptides by unnatural oligomers: antimicrobial beta-peptides. J. Am. Chem. Soc. 124(25):7324-30. doi:10.1021/ja0260871
  • Daniels DS, Petersson EJ, Qiu JX, Schepartz A (2007). "High-Resolution Structure of a β-Peptide Bundle". J. Am. Chem. Soc. 129,: 1532–1533. doi:doi:10.1021/ja068678n.

See also

  • Peptidomimetic
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Beta-peptide". A list of authors is available in Wikipedia.
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