Share This Article:

A Theoretical Study of β-Amino Acid Conformational Energies and Solvent Effect

Abstract Full-Text HTML XML Download Download as PDF (Size:651KB) PP. 122-131
DOI: 10.4236/ojpc.2015.54013    3,443 Downloads   4,097 Views   Citations


The conformations of four β-amino acids in a model peptide environment were investigated using Hartree-Fock (HF) and density functional theory (DFT) methods in gas phase and with solvation. Initial structures were obtained by varying dihedral angles in increments of 45° in the range 0° - 360°. Stable geometries were optimized at both levels of theory with the correlation consistent double-zeta basis set with polarization functions (cc-pVDZ). The results suggest that solvation generally stabilizes the conformations relative to the gas phase and that intramolecular hydrogen bonding may play an important role in the stability of the conformations. The β3 structures, in which the R-group of the amino acid is located on the carbon atom next to the N-terminus, are somewhat more stable relative to each other than the β2 structures which have the R-group on the carbon next to the carbonyl.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Waingeh, V. , Ngassa, F. and Song, J. (2015) A Theoretical Study of β-Amino Acid Conformational Energies and Solvent Effect. Open Journal of Physical Chemistry, 5, 122-131. doi: 10.4236/ojpc.2015.54013.


[1] Bestian, H. (1968) Poly-β-Amides. Angewandte Chemie International Edition in English, 7, 278-285.
[2] Glickson, J.D. and Applequist, J. (1971) The Conformation of Poly-β-Alanine in Aqueous Solution from Proton Magnetic Resonance and Deuterium Exchange Studies. Journal of the American Chemical Society, 93, 3276-3281.
[3] Kovacs, J., Ballina, R., Rodin, R.L., Balasubramanian, D. and Applequist, J. (1965) Poly-β-L-Aspartic Acid. Synthesis through Pentachlorophenyl Active Ester and Conformational Studies. Journal of the American Chemical Society, 87, 119-120.
[4] Dado, G.P. and Gellman, S.H. (1994) Redox Control of Secondary Structure in a Designed Peptide. Journal of American Chemical Society, 115, 12609-12610.
[5] Narita, M., Doi, M., Kudo, K. and Terauchi, Y. (1986) Conformations in the Solid State and Solubility Properties of Protected Homooligopeptides of Glycine and Beta-Alanine. Bulletin of Chemical Society of Japan, 59, 3553-3557.
[6] Yuki, H., Okamoto, Y., Taketani, Y., Tsubota, T. and Marubayshi, Y. (1978) Poly(β-Amino Acid)s. IV. Synthesis and Conformational Properties of Poly(α-Isobutyl-L-Aspartate). Journal of Polymer Science Part A: Polymer Chemistry, 16, 2237-2251.
[7] Fernandez-Santin, J.M., Aymami, J., Rodrigues-Galan, A., Munoz-Guerra, S. and Subirana, J.A. (1984) Pseudo α-Helix from Poly(α-Isobutyl-L-aspartate), a Nylon-3 Derivative. Nature, 311, 53-54.
[8] Fernandez-Santin, J.M., Munoz-Guerra, S., Rodrigues-Galan, A., Aymami, J., Lloveras, J., Subrina, J.A., Giralt, E. and Ptak, M. (1987) Helical Conformations in Polyamide of the Nylon-3 Family. Macromolecules, 20, 62-68.
[9] Lopez-Carrasquero, F., Aleman, C. and Munoz-Guerra, S. (1995) Conformational Analysis of Helical Poly(β-L-Aspartate)s by IR Dichroism. Biopolymers, 36, 263-271.
[10] Appella, D.H., Barchi Jr., J.J., Durell, S.R. and Gellman, S.H. (1999) Formation of Short, Stable Helices in Aqueous Solution by β-Amino Acid Hexamers. Journal of American Chemical Society, 121, 2309-2310.
[11] Appella, D.H., Christianson, L.A., Karle, I.L., Powell, D.R. and Gellman, S.H. (1999) Synthesis and Characterization of Trans-2-Aminocyclohexanecarboxylic Acid Oligomers: An Unnatural Helical Secondary Structure and Implications for β-Peptide Tertiary Structure. Journal of the American Chemical Society, 121, 6206-6212.
[12] Appella, D.H., Christianson, L.A., Klein, D.A., Richards, M.R., Powell, D.R. and Gellman, S.H. (1999) Synthesis and Structural Characterization of Helix-Forming β-Peptides: Trans-2-Aminocyclopentanecarboxylic Acid Oligomers. Journal of the American Chemical Society, 121, 7574-7581.
[13] Barchi Jr., J.J., Huang, X., Appella, D.H., Christianson, L.A., Durell, S.R. and Gellman, S.H. (2000) Solution Conformations of Helix-Forming β-Amino Acid Homooligomers. Journal of the American Chemical Society, 122, 2711-2718.
[14] Krauthauser, S., Christianson, L.A., Powell, D.R. and Gellman, S.H. (1997) Antiparallel Sheet Formation in β-Peptide Foldamers: Effects of β-Amino Acid Substitution on Conformational Preference. Journal of the American Chemical Society, 119, 11719-11720.
[15] Wang, X., Espinosa, J.F. and Gellman, S.H. (2000) 12-Helix Formation in Aqueous Solution with Short β-Peptides Containing Pyrrolidine-Based Residues. Journal of the American Chemical Society, 122, 4821-4822.
[16] Seebach, D., Abele, S., Gademann, K., Guichard, G., Hintermann, T., Juan, B., Mathews, J.L. and Schreiber, J.V. (1998) Beta2- and Beta3-Peptides with Proteinaceous Side Chains: Synthesis and Solution Structures of the Constitutional Isomers, a Novel Helical Secondary Structure and the Influence of Solvation and Hydrophobic Interactions on Folding. Helvetica Chimica Acta, 81, 932-982.
[17] Seebach, D., Ciceri, P., Overhand, M., Juan, B., Rigo, D., Oberer, L., Hommel, U., Amstutz, R. and Widmer, H. (1996) Probing the Helical Secondary Structure of Short-Chain-Beta-Peptides. Helvetica Chimica Acta, 79, 2043-2066.
[18] Seebach, D. and Mathews, J.L. (1997) Beta-Peptides: A Surprise at Every Turn. Chemical Communications, No. 21, 2015-2022.
[19] Seebach, D., Schreiber, J.V., Abele, S., Daura, X. and van Gunsteren, W.F. (2000) Structure and Conformation of β-Oligopeptide Derivatives with Simple Proteinogenic Side Chains: Circular Dichroism and Molecular Dynamics Investigations. Helvetica Chimica Acta, 83, 34-57.<34::AID-HLCA34>3.0.CO;2-B
[20] Banerjee, A. and Balaram, P. (1997) Stereochemistry of Peptides and Polypeptides Containing Omega Amino Acids. Current Science, 73, 1067-1077.
[21] Nelson, J.C., Saven, J.G., Moore, J.S. and Wolynes, P.G. (1997) Solvophobically Driven Folding of Nonbiological Oligomers. Science, 277, 1793-1796.
[22] Gellman, S.H. (1998) Foldamers: A Manifesto. Accounts of Chemical Research, 31, 173-180.
[23] Hayen, A., Schmitt, M.A., Ngassa, F.N., Thomasson, K.A. and Gellman, S.H. (2004) Two Helical Conformations from a Single Foldamer Backbone: “Split Personality” in Short Alpha/Beta-Peptides. Angewandte Chemie, 43, 505-510.
[24] Hill, D.J., Mio, M.J., Prince, R.B., Hughes, T.S. and Moore, J.S. (2001) A Field Guide to Foldamers. Chemical Reviews, 101, 3893-4012.
[25] Porter, E.A., Wang, X., Lee, H.S., Weisblum, B. and Gellman, S.H. (2000) Non-Haemolytic Beta-Amino-Acid Oligomers. Nature, 404, 13.
[26] Porter, E.A., Weisblum, B. and Gellman, S.H. (2002) Mimicry of Host-Defense Peptides by Unnatural Oligomers: Antimicrobial Beta-Peptides. Journal of the American Chemical Society, 124, 7324-7330.
[27] Raguse, T.L., Porter, E.A., Weisblum, B. and Gellman, S.H. (2002) Structure-Activity Studies of 14-Helical Antimicrobial Beta-Peptides: Probing the Relationship between Conformational Stability and Antimicrobial Potency. Journal of the American Chemical Society, 124, 12774-12785.
[28] Werder, M., Hauser, H., Abele, S. and Seebach, D. (1999) Beta-Peptides as Inhibitors of Small-Intestinal Cholesterol and Fat Absorption. Helvetica Chimica Acta, 82, 1774-1783.<1774::AID-HLCA1774>3.0.CO;2-O
[29] DeGrado, W.F., Schneider, J.P. and Hamuro, Y. (1999) The Twists and Turns of Beta-Peptides. The Journal of Peptide Research: Official Journal of the American Peptide Society, 54, 206-217.
[30] Gung, B.W., Zou, D. and Miyahara, Y. (2000) Synthesis of a Hybrid Peptide with Both α- and β-Amino Acid Residues: Toward a New β-Sheet Nucleator. Tetrahedron, 56, 9739-9746.
[31] Hintermann, T. and Seebach, D. (1997) The Biological Stability of Beta-Peptides: No Interactions between Alpha- and Beta-Peptide Structures. Chimia, 51, 244-247.
[32] Kaminsky, J. and Jensen, F. (2007) Force Field Modeling of Amino Acid Conformational Energies. Journal of Chemical Theory and Computation, 3, 1774-1788.
[33] Cheng, R.P., Gellman, S.H. and DeGrado, W.F. (2001) Beta-Peptides: From Structure to Function. Chemical Reviews, 101, 3219-3232.
[34] Seebach, D., Beck, A.K. and Bierbaum, D.J. (2004) The World of Beta- and Gamma-Peptides Comprised of Homologated Proteinogenic Amino Acids and Other Components. Chemistry & Biodiversity, 1, 1111-1239.
[35] Qiu, J.X., Petersson, E.J., Matthews, E.E. and Schepartz, A. (2006) Toward Beta-Amino Acid Proteins: A Cooperatively Folded Beta-Peptide Quaternary Structure. Journal of the American Chemical Society, 128, 11338-11339.
[36] Schmidt, M.W., Baldridge, K.K., Boatz, J.A., Elbert, S.T., Gordon, M.S., Jensen, J.H., Koseki, S., Matsunaga, N., Nguyen, K.A., Su, S., Windus, T.L., Dupuis, M. and Montgomery, J.A. (1993) General Atomic and Molecular Electronics Structure System. Journal of Computational Chemistry, 14, 1347-1363.
[37] Hanwell, M.D., Curtis, D.E., Lonie, D.C., Vandermeersch, T., Zurek, E. and Hutchison, G.R. (2012) Avogadro: An Advanced Semantic Chemical Editor, Visualization, and Analysis Platform. Journal of Cheminformatics, 4, 17.

comments powered by Disqus

Copyright © 2018 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.