Lee, Ho-Jin Park, Hyun-Mee Lee, Kang-Bong 2024-01-21T01:35:46Z 2024-01-21T01:35:46Z 2021-09-05 2007-01 0301-4622 https://pubs.kist.re.kr/handle/201004/134782 The conformational preferences of azaphenylalanine-containing peptide were investigated using a model compound, Ac-azaPhe-NHMe with ab initio method at the HF/3-21G and HF/6-31G* levels, and the seven minimum energy conformations with trans orientation of acetyl group and the 4 minimum energy conformations with cis orientation of acetyl group were found at the HF/6-31G* level if their mirror images were not considered. An average backbone dihedral angle of the 11 minimum energy conformations is phi= +/- 91 degrees +/- 24 degrees, Psi =+/- 18 degrees +/- 10 degrees (or +/- 169 degrees +/- 8 degrees), corresponding to the i+2 position of beta-turn (delta(R)) or polyproline II (beta(P)) structure, respectively. The chi(1) angle in the aromatic side chain of azaPhe residue adopts preferentially between +/- 60 degrees and +/- 130 degrees, which reflect a steric hindrance between the N-terminal carbonyl group or the C-terminal amide group and the aromatic side chain with respect to the configuration of the acetyl group. These conformational preferences of Ac-azaPhe-NHMe predicted theoretically were compared with those of For-Phe-NHMe to characterize the structural role of azaPhe residue. Four tripeptides containing azaPhe residue, Boc-Xaa-azaPhe-Ala-OMe [Xaa=Gly(1), Ala(2), Phe(3), Asn(4)] were designed and synthesized to verify whether the backbone torsion angles of azaPhe reside are still the same as compared with theoretical conformations and how the preceding amino acids of azaPhe residue perturb the beta-turn skeleton in solution. The solution conformations of these tripeptide models containing azaPhe residue were determined in CDCl3 and DMSO solvents using NMR and molecular modeling techniques. The characteristic NOE patterns, the temperature coefficients of amide protons and small solvent accessibility for the azapeptides 1-4 reveal to adopt the beta-turn structure. The structures of azapeptides containing azaPhe residue from a restrained molecular dynamics simulation indicated that average dihedral angles [(01, Psi(1)), (phi(2), Psi(2))] of Xaa-azaPhe fragment in azapeptide, Boc-Xaa-azaPhe-Ala-OMe were [(-68 degrees, 135 degrees), (116 degrees, -1 degrees)], and this implies that the intercalation of an azaPhe residue in tripeptide induces the beta II-tum conformation, and the volume change of a preceding amino acid of azaPhe residue in tripeptides would not perturb seriously the backbone dihedral angle of beta-turn conformation. We believe such information could be critical in desiging useful molecules containing azaPhe residue for drug discovery and peptide engineering. (c) 2006 Published by Elsevier B.V. English ELSEVIER SCIENCE BV AZAAMINO ACID RESIDUE THROMBIN INHIBITORS CONFORMATIONAL PREFERENCE CONTAINING DIPEPTIDES AZAPROLINE RESIDUE PEPTIDE MODELS SIDE-CHAIN AMIDE AZAPEPTIDES PROLINE The beta-turn scaffold of tripeptide containing an azaphenylalanine residue Article 10.1016/j.bpc.2006.05.028 1 BIOPHYSICAL CHEMISTRY, v.125, no.1, pp.117 - 126 BIOPHYSICAL CHEMISTRY 125 1 117 126 scie scopus 000243372400011 2-s2.0-33750739736 Biochemistry & Molecular Biology Biophysics Chemistry, Physical Biochemistry & Molecular Biology Biophysics Chemistry Article AZAAMINO ACID RESIDUE THROMBIN INHIBITORS CONFORMATIONAL PREFERENCE CONTAINING DIPEPTIDES AZAPROLINE RESIDUE PEPTIDE MODELS SIDE-CHAIN AMIDE AZAPEPTIDES PROLINE azapeptide beta-turn NMR molecular dynamics