Effects of the Alternating Backbone Configuration on the Secondary Structure and Self-Assembly of β-Peptides

• DOI: 10.1021/ja063890c
• Publication Date: 2006-09-22T10:09:21Z
• Authors: Tamás A. Martinek; István M. Mándity; Lívia Fülöp; Gábor K. Tóth; Elemér Vass; Miklós Hollósi; Eniko Forró; Ferenc Fülöp
• Keywords: Magnetic Resonance Spectroscopy; Circular Dichroism; Amino Acids, Cyclic; Stereoisomerism; 01 natural sciences; Protein Structure, Secondary; 0104 chemical sciences; Solutions; Microscopy, Electron, Transmission; Cycloleucine; Amino Acid Sequence; Peptides

Heterochiral homo-oligomers with alternating backbone configurations were constructed by using the different enantiomers of the cis- and trans-2-aminocyclopentanecarboxylic acid (ACPC) monomers. Molecular modeling and the spectroscopic techniques (NMR, ECD, and VCD) unequivocally proved that the alternating heterochiral cis-ACPC sequences form an H10/12 helix, where extra stabilization can be achieved via the cyclic side chains. The ECD and TEM measurements, together with molecular modeling, revealed that the alternating heterochiral trans-ACPC oligomers tend to attain a polar-strand secondary structure in solution, which can self-assemble into nanostructured fibrils. The observations indicate that coverage of all the possible secondary structures (various helix types and strand-mimicking conformations) can be attained with the help of cyclic beta-amino acid diastereomers. A relationship has been established between the backbone chirality pattern and the prevailing secondary structure, which underlines the role of stereochemical control in the beta-peptide secondary structure design and may contribute to future biological applications.