Role of azaamino acid residue in β-turn formation and stability in designed peptide

H. J. Lee, I. A. Ahn, S. Ro, Kihang Choi, Y. S. Choi, Kang Bong Lee

Research output: Contribution to journalArticle

43 Citations (Scopus)

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 languageEnglish
Pages (from-to)35-46
Number of pages12
JournalJournal of Peptide Research
Volume56
Issue number1
DOIs
Publication statusPublished - 2000 Jul 17

Fingerprint

Peptides
Acids
Conformations
Dihedral angle
Infrared spectroscopy
Spectrum Analysis
Peptidomimetics
Molecular modeling
Molecular Dynamics Simulation
Intercalation
Scaffolds
Amides
Organic solvents
Molecular dynamics
Protons
Nuclear magnetic resonance
Temperature
Computer simulation
t-butyloxycarbonylphenylalanylalanine

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 journalArticle

Lee, H. J. ; Ahn, I. A. ; Ro, S. ; Choi, Kihang ; Choi, Y. S. ; Lee, Kang Bong. / Role of azaamino acid residue in β-turn formation and stability in designed peptide. In: Journal of Peptide Research. 2000 ; Vol. 56, No. 1. pp. 35-46.
@article{04d4e91e353d48319685de9e0bdb7931,
title = "Role of azaamino acid residue in β-turn formation and stability in designed peptide",
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.",
keywords = "β-turn, Ab initio calculation, Azapeptide, IR, Molecular dynamics, NMR",
author = "Lee, {H. J.} and Ahn, {I. A.} and S. Ro and Kihang Choi and Choi, {Y. S.} and Lee, {Kang Bong}",
year = "2000",
month = "7",
day = "17",
doi = "10.1034/j.1399-3011.2000.00717.x",
language = "English",
volume = "56",
pages = "35--46",
journal = "Chemical Biology and Drug Design",
issn = "1747-0277",
publisher = "Blackwell",
number = "1",

}

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 -