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The effect of β‐methylation on the conformation of α, β‐dehydrophenylalanine: a DFT study
Author(s) -
Broda Małgorzata A.,
Buczek Aneta,
Siodłak Dawid,
Rzeszotarska Barbara
Publication year - 2009
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.1137
Subject(s) - conformational isomerism , ramachandran plot , chemistry , steric effects , amide , stereochemistry , pharmacophore , methyl group , side chain , dihedral angle , ring (chemistry) , residue (chemistry) , peptide , protein structure , hydrogen bond , molecule , group (periodic table) , biochemistry , polymer , organic chemistry
Dehydroamino acids are non‐coded amino acids that offer unique conformational properties. Dehydrophenylalanine (ΔPhe) is most commonly used to modify bioactive peptides to constrain the topography of the phenyl ring in the side chain, which commonly serves as a pharmacophore. The Ramachandran maps (in the gas phase and in CHCl 3 mimicking environments) of ΔPhe analogues with methyl groups at the β position of the side chain as well as at the C ‐terminal amide were calculated using the B3LYP/6‐31 + G** method. Unexpectedly, β‐methylation alone results in an increase of conformational freedom of the affected ΔPhe residue. However, further modification by introducing an additional methyl group at C ‐terminal methyl amide results in a steric crowding that fixes the torsion angle ψ of all conformers to the value 123°, regardless of the Z or E position of the phenyl ring. The number of conformers is reduced and the accessible conformational space of the residues is very limited. In particular, ( Z )‐Δ(βMe)Phe with the tertiary C ‐terminal amide can be classified as the amino acid derivative that has a single conformational state as it seems to adopt only the β conformation. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.