Short model peptides having a high α‐helical tendency: Design and solution properties

Abstract

Secondary structure is not typically observed for small peptides in solution. Several of the properties of alpha-helical peptides are known which lead to the stabilization of the structure. The utilization of all the known factors important for alpha-helical stabilization in the design of model alpha-helical peptides (MAP) is reported. The peptides are based on the repeating eleven amino acid sequence, Glu-Leu-Leu-Glu-Lys-Leu-Leu-Glu-Lys-Leu-Lys (MAP1-11). The CD spectra of these peptides give evidence for more alpha-helical content than has been reported for any short peptide (less than 18 amino acids) to date. This alpha-helical tendency does not require the presence of lipid or reduced temperature. For instance, Suc-[Trp9]MAP9-3'' amide (5), a seventeen amino acid peptide has 100% and 80% alpha-helical contents at 1.7 x 10(-4) M and 1.7 x 10(-5) M, respectively. Suc-[Trp9]MAP2-11 amide (3), merely ten amino acids in length, is 51% alpha-helical at 1.7 x 10(-4) M in 0.1 M phosphate buffer at room temperature. In the presence of lipid or trifluoroethanol, the alpha-helical content of these peptides is increased. This series of peptides demonstrates the complimentarity of various secondary structure design principles and the extent to which structure can be induced in small linear peptides.