Positional effects on helical Ala-based peptides

Richard P. Cheng, Prashant Girinath, Yuta Suzuki, Hsiou Ting Kuo, Hao Chun Hsu, Wei Ren Wang, Po An Yang, Donald Gullickson, Cheng Hsun Wu, Marc J. Koyack, Hsien Po Chiu, Yi Jen Weng, Pier Hart, Bashkim Kokona, Robert Fairman, Tzu-En Lin, Olivia Barrett

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Helix-coil equilibrium studies are important for understanding helix formation in protein folding, and for helical foldamer design. The quantitative description of a helix using statistical mechanical models is based on experimentally derived helix propensities and the assumption that helix propensity is position-independent. To investigate this assumption, we studied a series of 19-residue Ala-based peptides, to measure the helix propensity for Leu, Phe, and Pff at positions 6, 11, and 16. Circular dichroism spectroscopy revealed that substituting Ala with a given amino acid (Leu, Phe, or Pff) resulted in the following fraction helix trend: KXaa16 > KXaa6 > KXaa11. Helix propensities for Leu, Phe, and Pff at the different positions were derived from the CD data. For the same amino acid, helix propensities were similar at positions 6 and 11, but much higher at position 16 (close to the C-terminus). A survey of protein helices revealed that Leu/Phe-Lys (i, i + 3) sequence patterns frequently occur in two structural patterns involving the helix C-terminus; however, these cases include a left-handed conformation residue. Furthermore, no Leu/Phe-Lys interaction was found except for the Lys-Phe cation-π interaction in two cases of Phe-Ala-Ala-Lys. The apparent high helix propensity at position 16 may be due to helix capping, adoption of a 310-helix near the C-terminus perhaps with Xaa-Lys (i, i + 3) interactions, or proximity to the peptide chain terminus. Accordingly, helix propensity is generally position-independent except in the presence of alternative structures or in the proximity of either chain terminus. These results should facilitate the design of helical peptides, proteins, and foldamers.

Original languageEnglish
Pages (from-to)9372-9384
Number of pages13
JournalBiochemistry
Volume49
Issue number43
DOIs
StatePublished - 2 Nov 2010

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