Chemistry:Beta-peptide
Beta-peptides (β-peptides) are peptides derived from β-amino acids, in which the amino group is attached to the β-carbon (i.e. the carbon two atoms away from the carboxylate group). The parent β-amino acid is β-alanine (H2NCH2CH2CO2H), a common natural substance, but most examples feature substituents in place of one or more C-H bonds. β-peptides usually do not occur in nature. β-peptide-based antibiotics are being explored as ways of evading antibiotic resistance.[1] Early studies in this field were published in 1996 by the group of Dieter Seebach[1] and that of Samuel Gellman.[2]
Structure
As there are two carbons 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.[3] Accordingly, two main types β-amino acids exist differing by which carbon the residue is attached to: ones with the organic residue (R) next to the amine are called β3 and those with position next to the carbonyl group are called β2. A β-peptide can consist of only one kind of these amino acids (β2-peptides and β3-peptides), or have a combination of the two. Furthermore, a β-amino acid can form a ring using both of its sites and also be incorporated into a peptide.[3]
Synthesis
β-Amino acids have been prepared by many routes,[4][5] 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,[6] and 10/12-helix have been reported. Generally speaking, β-peptides form a more stable helix than α-peptides.[7]
Clinical potential
β-peptides are stable against proteolytic degradation in vitro and in vivo, a potential advantage over natural peptides.[8] 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.[9]
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.[10]:23 Of these, β-alanine is found in mammals and incorporated in pantothenic acid, an essential nutrient.[10]:2 Two α-amino acids are also structurally β-amino acids: aspartic acid and asparagine.[10]:218 Microcystins are a class of compounds containing a β-isoaspartyl (i.e. aspartic acid linked with its beta-carboxyl) residue.[10]:23
See also
References
- ↑ 1.0 1.1 "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 79 (4): 913–941. June 1996. doi:10.1002/hlca.19960790402.
- ↑ "β-Peptide Foldamers: Robust Helix Formation in a New Family of -Amino Acid Oligomers". J. Am. Chem. Soc. 118 (51): 13071–2. 1996. doi:10.1021/ja963290l.
- ↑ 3.0 3.1 "β-Peptides: a surprise at every turn". Chem. Commun. (21): 2015–22. 1997. doi:10.1039/a704933a. https://chab.ethz.ch/content/dam/ethz/special-interest/chab/chab-dept/department/images/Emeriti/Seebach/PDFs/596_CC_1997.pdf.
- ↑ "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. November 2005. doi:10.1021/jo0515226. PMID 16292808.
- ↑ "Efficient synthesis of a β-peptide combinatorial library with microwave irradiation". J. Am. Chem. Soc. 127 (38): 13271–80. September 2005. doi:10.1021/ja052733v. PMID 16173757.
- ↑ Vasantha, Basavalingappa; George, Gijo; Raghothama, Srinivasarao; Balaram, Padmanabhan (January 2017). "Homooligomeric β3 (R)-valine peptides: Transformation between C14 and C12 helical structures induced by a guest Aib residue". Biopolymers 108 (1): e22935. doi:10.1002/bip.22935. ISSN 1097-0282. PMID 27539268. https://pubmed.ncbi.nlm.nih.gov/27539268. Retrieved 2022-05-07.
- ↑ "Beta-peptides: twisting and turning". Curr. Med. Chem. 6 (10): 905–25. October 1999. doi:10.2174/092986730610220401154606. PMID 10519905.
- ↑ "Toward a rational design of β-peptide structures". J Comput Chem 27 (1): 20–38. January 2006. doi:10.1002/jcc.20299. PMID 16247761.
- ↑ "Mimicry of host-defense peptides by unnatural oligomers: antimicrobial β-peptides". J. Am. Chem. Soc. 124 (25): 7324–30. 2002. doi:10.1021/ja0260871. PMID 12071741.
- ↑ 10.0 10.1 10.2 10.3 Juaristi, E.; Soloshonok, Vadim A. (6 May 2005). Enantioselective Synthesis of Beta-Amino Acids. Hoboken, New Jersey (NJ): Wiley Inc.. ISBN 9780471698470. OCLC 559972352. https://books.google.com/books?id=WpgRvHGa0zIC&dq=8%20beta%20forms&pg=PA23. Retrieved 7 May 2022.
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