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?-Helix mimicry with ?/?-peptides.

ABSTRACT: We describe a general strategy for creating peptidic oligomers that have unnatural backbones but nevertheless adopt a conformation very similar to the ?-helix. These oligomers contain both ?- and ?-amino acid residues (?/?-peptides). If the ? content reaches 25-30% of the residue total, and the ? residues are evenly distributed along the backbone, then substantial resistance to proteolytic degradation is often observed. These ?/?-peptides can mimic the informational properties of ?-helices involved in protein-protein recognition events, as documented in numerous crystal structures. Thus, these unnatural oligomers can be a source of antagonists of undesirable protein-protein interactions that are mediated by natural ?-helices, or agonists of receptors for which the natural polypeptide ligands are ?-helical. Successes include mimicry of BH3 domains found in proapoptotic proteins, which leads to ligands for antiapoptotic Bcl-2 family proteins, and mimicry of the gp41 CHR domain, which leads to inhibition of HIV infection in cell-based assays.

SUBMITTER: Johnson LM

PROVIDER: S-EPMC3928965 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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α-Helix mimicry with α/β-peptides.

Johnson Lisa M LM Gellman Samuel H SH

Methods in enzymology 20130101

We describe a general strategy for creating peptidic oligomers that have unnatural backbones but nevertheless adopt a conformation very similar to the α-helix. These oligomers contain both α- and β-amino acid residues (α/β-peptides). If the β content reaches 25-30% of the residue total, and the β residues are evenly distributed along the backbone, then substantial resistance to proteolytic degradation is often observed. These α/β-peptides can mimic the informational properties of α-helices invol ...[more]

PMID: 23422441

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