Positional Effects on Helical Ala-Based Peptides

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• 作者：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 ; Bashk
• 刊名：Biochemistry
• 出版年：2010
• 出版时间：November 2, 2010
• 年：2010
• 卷：49
• 期：43
• 页码：9372-9384
• 全文大小：1150K
• 年卷期：v.49,no.43(November 2, 2010)
• ISSN：1520-4995

文摘

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.