Residue-Based Control of Helix Shape in (-Peptide Foldamers. Douglas R. Powell^a, Daniel H. Appella^a, Laurie A. Christianson^a, Daniel A. Klein^a, Xiaolin Huang^b, Joseph J. Barchi, Jr.^b, and Samuel H. Gellman^a, ^aDepartment of Chemistry, University of Wisconsin, Madison, WI 53706, ^bLaboratory of Medicinal Chemistry, Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892

Folding is linked to function in both proteins and RNA. Thus, access to new types of polymeric backbones with well-defined and predictable folding propensities ("foldamers") could lead to development of molecules with unique and useful functions. Recently polymers constructed from (-substituted (-amino acids¹ or trans-2-aminocyclohexanecarboxylic acids² were shown to form helices with 14-membered, hydrogen bond rings. We report that (-peptides formed from trans-2-aminocyclopentanecarboxylic acids form helices with 12-membered, hydrogen bond rings in the opposite direction from the previous 14-helix (-peptides. This finding shows that (-peptides allow profound residue-based control of conformation.

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