Beta-peptide

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File:Beta alanine comparison.png
Figure 1: β-alanine, an example of a β amino acid. The amino group attaches not to the α carbon but to the β carbon, which in this case is the sidechain methylene.

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.

Chemical structure and synthesis

In α 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 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 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 atom. A number of synthesis mechanisms have been introduced to efficiently form β amino acids and their derivatives[1][2].

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 [3].

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 [4]. 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 [5].

Further reading

  1. ^  Gademann K, Hintermann T, Schreiber JV. (1999). "Beta-peptides: twisting and turning.", Curr Med Chem Oct;6(10):905-25. [6].
  2. ^  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. [7].
  3. ^  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 Soc127(38):13271-80. [8]
  4. ^  Beke T, Somlai C, Perczel A. (2006). "Toward a rational design of beta-peptide structures.", J Comp Chem Jan 15;27(1):20-38. [9].
  5. ^  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.

See also


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