Azido gauche effect on the backbone conformation of β-azidoalanine peptides

Kwang Im Oh, Woosung Kim, Cheonik Joo, Dong Geun Yoo, Hogyu Han, Geum Sook Hwang, Minhaeng Cho

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24 Citations (Scopus)


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 (PII) 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 PII 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 C 7/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 PII nor right-handed α-helix (αR) 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 C 7-conformation-directing element, which may also be useful for tuning the structures of other amino acids and polypeptides.

Original languageEnglish
Pages (from-to)13021-13029
Number of pages9
JournalJournal of Physical Chemistry B
Issue number40
Publication statusPublished - 2010 Oct 14

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry


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