Short, solubilized polyalanines are conformational chameleons: Exceptionally helical if N- and C-capped with helix stabilizers, weakly to moderately helical if capped with rigid spacers

Isolating spacers introduced between solubilizing lysine regions and a poly alanine core permit rigorous characterization of context-free alanine helic es. The preferred building blocks for isolating spacers are amino acids wit h rigid, extended conformations such as proline, isonipecotic acid, and ter t-leucine. Replacing isolating spacers by conventional N- and C-caps dramat ically increases the helicity of dodecaalanine. Solubilized, isolated polya lanines provide optimal tools for testing polypeptide helicity algorithms, central to resolution of the protein folding problem.