The effect of beta-methylation on the conformation of alpha, beta-dehydrophenylalanine: a DFT study.
Dehydroamino acids are non-coded amino acids that offer unique conformational properties. Dehydrophenylalanine (DeltaPhe) 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 DeltaPhe analogues with methyl groups at the beta position of the side chain as well as at the C-terminal amide were calculated using the B3LYP/6-31 + G** method. Unexpectedly, beta-methylation alone results in an increase of conformational freedom of the affected DeltaPhe 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 psi of all conformers to the value 123 degrees , 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)-Delta(betaMe)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 beta conformation.
Broda
Małgorzata A
MA
Institute of Chemistry, University of Opole, Opole, Poland. małgorzata.broda@uni.opole.pl
Buczek
Aneta
A
Siodłak
Dawid
D
Rzeszotarska
Barbara
B
D008745:Methylation; D008968:Molecular Conformation; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry; D011789:Quantum Theory; D013329:Structure-Activity Relationship
D010649:Phenylalanine; C018632:phenyldehydroalanine