Abstract
The structural perturbation induced by C(α)H→N(α) exchange in azaamino acid-containing peptides was predicted by ab initio calculation of the 6-31G* and 3-21G* levels. The global energy-minimum conformations for model compounds, For-azaXaa-NH2 (Xaa=Gly, Ala, Leu) appeared to be the β- turn motif with a dihedral angle of Φ = ±90°, ψ =0°. This suggests that incorporation of the azaXaa residue into the i+2 position of designed peptides could stabilize the β-turn structure. The model azaLeu-containing peptide, Boc-Phe-azaLeu-Ala-OMe, which is predicted to adopt a β-turn conformation was designed and synthesized in order to experimentally elucidate the role of the azaamino acid residue. Its structural preference in organic solvents was investigated using 1H NMR, molecular modelling and IR spectroscopy. The temperature coefficients of amide protons, the characteristic NOE patterns, the restrained molecular dynamics simulation and, IR spectroscopy defined the dihedral angles [ (Φi+1, ψi+1) (Φi+2, ψi+2)] of the Phe-azaLeu fragment in the model peptide, Boc-Phe-azaLeu-Ala- OMe, as [(-59°, 127°) (107°, -4°)]. This solution conformation supports a βII-turn structural preference in azaLeu-containing peptides as predicted by the quantum chemical calculation. Therefore, intercalation of the azaamino acid residue into the i+2 position in synthetic peptides is expected to provide a stable β-turn formation, and this could be utilized in the design of new peptidomimetics adopting a β-turn scaffold.
| Original language | English |
|---|---|
| Pages (from-to) | 35-46 |
| Number of pages | 12 |
| Journal | Journal of Peptide Research |
| Volume | 56 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2000 Jul 17 |
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Keywords
- β-turn
- Ab initio calculation
- Azapeptide
- IR
- Molecular dynamics
- NMR
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
Cite this
Role of azaamino acid residue in β-turn formation and stability in designed peptide. / Lee, H. J.; Ahn, I. A.; Ro, S.; Choi, Kihang; Choi, Y. S.; Lee, Kang Bong.
In: Journal of Peptide Research, Vol. 56, No. 1, 17.07.2000, p. 35-46.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of azaamino acid residue in β-turn formation and stability in designed peptide
AU - Lee, H. J.
AU - Ahn, I. A.
AU - Ro, S.
AU - Choi, Kihang
AU - Choi, Y. S.
AU - Lee, Kang Bong
PY - 2000/7/17
Y1 - 2000/7/17
N2 - The structural perturbation induced by C(α)H→N(α) exchange in azaamino acid-containing peptides was predicted by ab initio calculation of the 6-31G* and 3-21G* levels. The global energy-minimum conformations for model compounds, For-azaXaa-NH2 (Xaa=Gly, Ala, Leu) appeared to be the β- turn motif with a dihedral angle of Φ = ±90°, ψ =0°. This suggests that incorporation of the azaXaa residue into the i+2 position of designed peptides could stabilize the β-turn structure. The model azaLeu-containing peptide, Boc-Phe-azaLeu-Ala-OMe, which is predicted to adopt a β-turn conformation was designed and synthesized in order to experimentally elucidate the role of the azaamino acid residue. Its structural preference in organic solvents was investigated using 1H NMR, molecular modelling and IR spectroscopy. The temperature coefficients of amide protons, the characteristic NOE patterns, the restrained molecular dynamics simulation and, IR spectroscopy defined the dihedral angles [ (Φi+1, ψi+1) (Φi+2, ψi+2)] of the Phe-azaLeu fragment in the model peptide, Boc-Phe-azaLeu-Ala- OMe, as [(-59°, 127°) (107°, -4°)]. This solution conformation supports a βII-turn structural preference in azaLeu-containing peptides as predicted by the quantum chemical calculation. Therefore, intercalation of the azaamino acid residue into the i+2 position in synthetic peptides is expected to provide a stable β-turn formation, and this could be utilized in the design of new peptidomimetics adopting a β-turn scaffold.
AB - The structural perturbation induced by C(α)H→N(α) exchange in azaamino acid-containing peptides was predicted by ab initio calculation of the 6-31G* and 3-21G* levels. The global energy-minimum conformations for model compounds, For-azaXaa-NH2 (Xaa=Gly, Ala, Leu) appeared to be the β- turn motif with a dihedral angle of Φ = ±90°, ψ =0°. This suggests that incorporation of the azaXaa residue into the i+2 position of designed peptides could stabilize the β-turn structure. The model azaLeu-containing peptide, Boc-Phe-azaLeu-Ala-OMe, which is predicted to adopt a β-turn conformation was designed and synthesized in order to experimentally elucidate the role of the azaamino acid residue. Its structural preference in organic solvents was investigated using 1H NMR, molecular modelling and IR spectroscopy. The temperature coefficients of amide protons, the characteristic NOE patterns, the restrained molecular dynamics simulation and, IR spectroscopy defined the dihedral angles [ (Φi+1, ψi+1) (Φi+2, ψi+2)] of the Phe-azaLeu fragment in the model peptide, Boc-Phe-azaLeu-Ala- OMe, as [(-59°, 127°) (107°, -4°)]. This solution conformation supports a βII-turn structural preference in azaLeu-containing peptides as predicted by the quantum chemical calculation. Therefore, intercalation of the azaamino acid residue into the i+2 position in synthetic peptides is expected to provide a stable β-turn formation, and this could be utilized in the design of new peptidomimetics adopting a β-turn scaffold.
KW - β-turn
KW - Ab initio calculation
KW - Azapeptide
KW - IR
KW - Molecular dynamics
KW - NMR
UR - http://www.scopus.com/inward/record.url?scp=0033918938&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033918938&partnerID=8YFLogxK
U2 - 10.1034/j.1399-3011.2000.00717.x
DO - 10.1034/j.1399-3011.2000.00717.x
M3 - Article
C2 - 10917455
AN - SCOPUS:0033918938
VL - 56
SP - 35
EP - 46
JO - Chemical Biology and Drug Design
JF - Chemical Biology and Drug Design
SN - 1747-0277
IS - 1
ER -