Beta-peptide 1128773 192998325 2008-02-21T08:51:44Z Sneugle 660949 /* References */ removed dupe [[Image:Beta-alanineVSalpha-alanine.png|400px|right|β-alanine, an example of a β amino acid. The amino group attaches not to the &alpha; 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|amino group]] bonded to the [[β carbon]] rather than the &alpha; carbon as in the 20 standard biological [[amino acid]]s. The only commonly naturally occurring β amino acid is [[beta-alanine|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]] <ref>''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}}</ref> and that of Gellman <ref>''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}} </ref>. ==Chemical structure and synthesis== In &alpha; amino acids (molecule at left), both the [[carboxylic acid]] group (red) and the [[amino]] group (blue) are bonded to the same carbon, termed the &alpha; carbon (<math>\mathrm{C}^{\alpha}</math>) because it is one atom away from the carboxylate group. In β amino acids, the amino group is bonded to the β carbon (<math>\mathrm{C}^{\beta}</math>), 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 group]]s bonded to the β carbon and the necessity of maintaining [[Chirality (chemistry)|chirality]]. In the [[alanine]] molecule shown, the β carbon is achiral; however, most larger amino acids have a chiral <math>\mathrm{C}^{\beta}</math> atom. A number of synthesis mechanisms have been introduced to efficiently form β amino acids and their derivatives<ref>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}} [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=16292808%5BUID%5D].</ref><ref>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}}[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=16173757%5BUID%5D]</ref> 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 β<sup>3</sup>-peptides and those with position next to the carbonyl group are called β<sup>2</sup>-peptides <ref>''β-Peptides: a surprise at every turn'' [[Dieter Seebach]] and Jennifer L. Matthews [[Chem. Commun.]], '''1997''', (21),2015-2022 {{DOI|10.1039/a704933a}} </ref>. :[[Image:Beta-peptides.png|400px|Beta peptides]] ==Secondary Structure== Because the backbones of β-peptides are longer than those of [[peptide]]s that consist of &alpha;-amino acids, β-peptides form different [[secondary structure]]s. The [[alkyl]] [[substituent]]s at both the &alpha; and β positions in a β amino acid favor a [[gauche conformation]] about the bond between the &alpha;-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 bond|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 &alpha;-peptides <ref>Gademann K, Hintermann T, Schreiber JV. (1999). "Beta-peptides: twisting and turning.", ''Curr Med Chem'' Oct;6(10):905-25. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=10519905%5BUID%5D].</ref>. The β-peptide ''zwit-1F'' with a fully described [[quaternary structure]] <ref>''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}} </ref> is called a '''β-protein''' because it has many characteristics of an actual [[protein]]. Eight 12-helix units [[self-assembly|self-assemble]] in water to a superstructure with a hydrophobic inner core. ==Clinical potential== β-peptides are stable against [[Proteolysis|proteolytic degradation]] [[in vitro]] and [[in vivo]], an important advantage over natural peptides in the preparation of peptide-based drugs <ref>Beke T, Somlai C, Perczel A. (2006). "Toward a rational design of beta-peptide structures.", ''J Comp Chem'' Jan 15;27(1):20-38. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=16247761%5BUID%5D].</ref>. &beta;-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 <ref>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}}</ref>. ==References== <div class="references-small"><references /></div> ==See also== *[[Peptidomimetic]] [[Category:Peptides]]