Azido Gauche Effect on the Backbone Conformation of β-Azidoalanine Peptides

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• 作者：Kwang-Im Oh ; Woosung Kim ; Cheonik Joo ; Dong-Geun Yoo ; Hogyu Han ; Geum-Sook Hwang ; Minhaeng Cho
• 刊名：Journal of Physical Chemistry B
• 出版年：2010
• 出版时间：October 14, 2010
• 年：2010
• 卷：114
• 期：40
• 页码：13021-13029
• 全文大小：420K
• 年卷期：v.114,no.40(October 14, 2010)
• ISSN：1520-5207

文摘

To study the azido gauche effect on the backbone conformation of β-azidoalanine (Aza) dipeptide (AAD, Ac-Aza-NHMe) and tripeptide (AAT, Ac-Aza-Aza-NH₂), we used spectroscopic methods in combination with quantum chemistry calculations and molecular dynamics (MD) simulations. From the ¹H NMR coupling constants and ¹H,¹H NOESY experimental data, we found that AAD in water mainly adopts a seven-membered cyclic (C₇) rather than polyproline II (P_II) backbone conformation and prefers the gauche− (g⁻) side-chain conformer. From the amide I IR absorption and circular dichroism (CD) spectra, the backbone conformation of AAD in water is found to deviate from P_II but is rather close to C₇. Thus, the backbone conformation of AAD differs from that of alanine dipeptide (AD, Ac-Ala−NHMe), which is mainly P_II in water. The underlying origin of the backbone conformational difference between AAD and AD in water was elucidated by quantum chemistry calculations with density functional theory (DFT). It was found that the C₇/g⁻ conformer is the lowest energy structure of an isolated AAD. Here, the β-azido group forms intramolecular electrostatic interactions with two neighboring peptide bonds, which are facilitated by the azido gauche effect. Thus, the β-azido group appears to be responsible for directing the peptide backbone conformation toward the C₇ structure. The quantum mechanical/molecular mechanical (QM/MM) MD simulations show that AAD in water adopts neither P_II nor right-handed α-helix (α_R) and prefers the g⁻ conformer. Thus, the intramolecular electrostatic interactions between the β-azido group and two nearby peptide bonds are also found even in the aqueous solution structure of AAD. Consequently, the β-azido group appears to be an effective C₇-conformation-directing element, which may also be useful for tuning the structures of other amino acids and polypeptides.