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

• Published in: Journal of the American Chemical Society 2006-10, Vol.128 (41), p.13539-13544
• Main Authors: Martinek, Tamás A, Mándity, István M, Fülöp, Lívia, Tóth, Gábor K, Vass, Elemér, Hollósi, Miklós, Forró, Eniko, Fülöp, Ferenc
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino Acids, Cyclic - chemistry; Chemistry; Circular Dichroism; Cycloleucine - analogs & derivatives; Cycloleucine - chemistry; Exact sciences and technology; General and physical chemistry; Magnetic Resonance Spectroscopy; Microscopy, Electron, Transmission; Organic chemistry; Peptides; Peptides - chemistry; Preparations and properties; Protein Structure, Secondary; Solutions - chemistry; Stereoisomerism
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja063890c

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 β-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 β-peptide secondary structure design and may contribute to future biological applications.