This MedLibrary.org supplementary page on Beta-peptide is provided directly from the open source Wikipedia as a service to our readers. Please see the note below on authorship of this content, as well as the Wikipedia usage guidelines. To search for other content from our encyclopedia supplement, please use the form below:
Related Sponsors
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.
Contents |
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 derivatives34 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.
References
- ^ 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
- ^ 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
- ^ 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].
- ^ 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]
- ^ β-Peptides: a surprise at every turn Dieter Seebach and Jennifer L. Matthews Chem. Commun., 1997, (21),2015-2022 doi:10.1039/a704933a
- ^ Gademann K, Hintermann T, Schreiber JV. (1999). "Beta-peptides: twisting and turning.", Curr Med Chem Oct;6(10):905-25. [3].
- ^ 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
- ^ 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].
- ^ 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
See also
Wikipedia content modification information:
- This page was last modified on 21 February 2008, at 08:51.
Wikipedia Authorship and Review
Wikipedia content provided here is not reviewed directly by MedLibrary.org. Wikipedia content is authored by an open community of volunteers and is not produced by or in any way affiliated with MedLibrary.org.
Wikipedia Usage Guidelines
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article on "Beta-peptide".
The URL for this specific entry is:
All Wikipedia text is available under the terms of the GNU Free Documentation License. (See Copyrights for details). Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc.