Helix formation in alpha,gamma- and beta,gamma-hybrid peptides: theoretical insights into mimicry of alpha- and beta-peptides.
Alpha,gamma- and beta,gamma-hybrid peptides, which are composed of two different homologous amino acid constituents in alternate order, are suggested as novel classes of peptide foldamers. On the basis of a systematic conformational search employing the methods of ab initio MO theory, the possibilities for the formation of periodic secondary structures in these systems are described. The conformational analysis provides a great number of helix conformers widely differing in energy, which can be arranged into three groups: (i) helices with all hydrogen bonds formed in forward direction along the sequence, (ii) helices with all hydrogen bonds in backward direction, and (iii) helices with alternate hydrogen-bond directions (mixed or beta-helices). Most stable are representatives of beta-helices, but their stability decreases considerably in more polar environments in comparison to helix conformers from the other two classes. There is a great similarity between the overall topology of the most stable hybrid peptide helices and typical helices of peptides which are exclusively composed of a single type of homologous amino acids. Thus, the helices of the beta,gamma-hybrid peptides mimic perfectly those of the native alpha-peptides as, for instance, the well-known alpha-helix, whereas the most stable helix conformers of alpha,gamma-hybrid peptides correspond well to the overall structure of beta-peptide helices. The two suggested novel hybrid peptide classes expand considerably the pool of peptide foldamers and may be promising tools in peptide design and in material sciences.
Baldauf
Carsten
C
Institute of Biochemistry, Faculty of Biosciences, Pharmacy, and Psychology, University of Leipzig, Brüderstrasse 34, D-04103 Leipzig, Germany.
Günther
Robert
R
Hofmann
Hans-Jörg
HJ
D000596:Amino Acids / Q000737:chemistry*; D040761:Biomimetic Materials / Q000737:chemistry*; D019295:Computational Biology; D019281:Dimerization; D006860:Hydrogen Bonding; D008958:Models, Molecular; D017433:Protein Structure, Secondary
D000596:Amino Acids