Helix formation and preferences in a/b-peptide oligomers

ORGN 495

Margaret A. Schmitt, Ahlke Hayen, and Samuel H. Gellman. Dept. of Chemistry, University of Wisconsin, 1101 University Ave., Madison, WI 53706
Oligomers that adopt predictable conformations (“foldamers”) are subjects of increasing interest. Most foldamers reported to date have homogeneous backbones. We show that combining a-amino acid and cyclic b-amino acid residues in a sequentially alternating pattern can lead to helix formation within relatively short heterooligomers. Structural data suggest that these foldamers have a "split personality," simultaneously populating two different helical conformations and displaying a length-dependent shift in the percentage of each conformation adopted. This behavior parallels closely the split personality observed among peptides composed exclusively of a-amino acid residues, which frequently populate both a- and 310-helical conformations in solution. The different monomer types in the heterogeneous backbone offer complementary benefits to these new foldamers: the b-residues provide conformational preorganization, while the a-residues allow introduction of specific sidechains at specific positions.