Beta-peptide

Structure

As there are two carbon atoms available for substitution, β-amino acids have four sites (chirality included; as opposed to two in α-amino acids) for attaching the organic residue group.

Synthesis

β-Amino acids have been prepared by many routes, including some based on the Arndt-Eistert synthesis.

Secondary structure

Because their backbones are longer than those of normal peptides, β-peptides form disparate 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, a potential advantage over natural peptides. 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.

Examples

β-Amino acids with a wide variety of substituents exist. Named by analogy to the biological α-amino acids, the following have been found naturally: β-alanine, β-leucine, β-lysine, β-arginine, β-glutamate, β-glutamine, β-phenylalanine and β-tyrosine. Of these, β-alanine is found in mammals and incorporated in pantothenic acid, an essential nutrient. Aspartic acid is structurally a β-amino acids. Microcystins are a class of compounds containing a β-isoaspartyl (i.e. aspartic acid linked with its beta-carboxyl) residue.

References

References

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2. (1996). "β-Peptide Foldamers: Robust Helix Formation in a New Family of -Amino Acid Oligomers". [[J. Am. Chem. Soc.]].
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5. (September 2005). "Efficient synthesis of a β-peptide combinatorial library with microwave irradiation". J. Am. Chem. Soc..
6. (January 2017). "Homooligomeric β3 (R)-valine peptides: Transformation between C14 and C12 helical structures induced by a guest Aib residue". Biopolymers.
7. (October 1999). "Beta-peptides: twisting and turning". Curr. Med. Chem..
8. (January 2006). "Toward a rational design of β-peptide structures". J Comput Chem.
9. (2002). "Mimicry of host-defense peptides by unnatural oligomers: antimicrobial β-peptides". [[J. Am. Chem. Soc.]].
10. (6 May 2005). "Enantioselective Synthesis of Beta-Amino Acids". Wiley Inc..