Foldameric α/β-Peptide Analogs of the β-Sheet-Forming Antiangiogenic Anginex: Structure and Bioactivity

• DOI: 10.1021/ja408054f
• Publication Date: 2013-10-02T16:13:22Z
• Authors: Zsófia Hegedüs; Edit Wéber; Éva Kriston-Pál; Ildikó Makra; Ágnes Czibula; Éva Monostori; Tamás A. Martinek
• Keywords: Beta sheet; Folding (DSP implementation); Foldamer

The principles of β-sheet folding and design for α-peptidic sequences are well established, while those sheet mimetics containing homologated amino acid building blocks still under investigation. To reveal the structure–function relations β-amino-acid-containing foldamers, we followed a top-down approach to study series α/β-peptidic analogs anginex, β-sheet-forming antiangiogenic peptide. Eight anginex were developed by systematic α → β3 substitutions analyzed using NMR CD spectroscopy. foldamers retained tendency, though with decreased propensity. β-Sheet formation could be induced micellar environment, similarly that parent destructuring effect was higher when exchange located in core. Analysis stability versus substitution pattern local conformational bias bulky β3V β3I residues revealed mismatch between H-bonding preferences α- β-residues played minor role structure-breaking effect. Temperature-dependent measurements showed hydrophobic stabilization scaled-down α/β-peptides. biological activity foldamer peptides four derivatives dose-dependently inhibited proliferation mouse endothelial cell line. strategy applied this work can useful construction bioactive reduced aggregation tendency improved pharmacokinetic properties.