Residue-based control of helix shape in β-peptide oligomers

• Published in: Nature (London) 1997-05, Vol.387 (6631), p.381-384
• Main Authors: Appella, Daniel H, Christianson, Laurie A, Klein, Daniel A, Powell, Douglas R, Huang, Xiaolin, Barchi, Joseph J, Gellman, Samuel H
• Format: Article
• Language: English
• Subjects: Amino acids; Amino Acids - chemistry; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Biopolymers; Catalysis; Chemistry; Circular Dichroism; Cyclohexanecarboxylic Acids - chemistry; Cyclohexylamines - chemistry; Cycloleucine - analogs & derivatives; Cycloleucine - chemistry; Fundamental and applied biological sciences. Psychology; General aspects, investigation methods; Humanities and Social Sciences; letter; Magnetic Resonance Spectroscopy; Models, Molecular; multidisciplinary; Oligopeptides - chemistry; Peptides; Polymers; Protein Folding; Protein Structure, Secondary; Proteins; Science; Science (multidisciplinary)
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/387381a0

Proteins and RNA are unique among known polymers in their ability to adopt compact and well-defined folding patterns. These two biopolymers can perform complex chemical operations such as catalysis and highly selective recognition, and these functions are linked to folding in that the creation of an active site requires proper juxtaposition of reactive groups. So the development of new types of polymeric backbones with well-defined and predictable folding propensities ('foldamers') might lead to molecules with useful functions 1,2 . The first step in foldamer development is to identify synthetic oligomers with specific secondary structural preferences 3–13 . Whereas α-amino acids can adopt the well-known α-helical motif of proteins, it was shown recently 11–13 that β-peptides 3 constructed from carefully chosen β-amino acids can adopt a different, stable helical conformation defined by interwoven 14-membered-ring hydrogen bonds (a 14-helix; Fig. la). Here we report that β-amino acids can also be used to design β-peptides with a very different secondary structure, a 12-helix (Fig. la). This demonstrates that by altering the nature of β-peptide residues, one can exert rational control over the secondary structure.