Cover image for Vol. 16 Issue 13

Editor: Peter Gölitz; Editorial Board Chairs: Thomas Carell, Donald Hilvert, Barbara Imperiali

Online ISSN: 1439-7633

Associated Title(s): ChemCatChem, ChemMedChem, ChemPhysChem, ChemSusChem

12_13/2011Cover Picture: Structural Basis of Bcl-xL Recognition by a BH3-Mimetic α/β-Peptide Generated by Sequence-Based Design (ChemBioChem 13/2011)

The cover picture shows representations of death-inducing BH3 peptides in complex with the anti-apoptotic protein Bcl-xL. Of the four structures, three are naturally occurring BH3 peptides comprising only α-amino acids. However, one of them is a designer α/β-peptide containing β-amino acid residues distributed periodically throughout the sequence. (Question: Can you spot the difference?) Such unnatural backbones are less susceptible to enzymatic degradation than their α-peptide counterparts, thus making them more appealing for use in biological systems. The structure described by S. H. Gellman, W. D. Fairlie et al. on p. 2025 ff. demonstrates that side chains from this α/β-peptide successfully mimic the noncovalent interactions previously identified as critical for binding prosurvival proteins. Further geometric analysis reveals the mechanism by which the α/β-peptide backbone recapitulates the multipoint interaction of the α-helical prototype. Such structural studies provide useful insights into successful α-helix mimicry with sequence-based design strategies. (Answer: The α/β-peptide is in the bottom right panel.)

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