The binding of the phenytoin (5,5-diphenyl-2,4-imidazolidinedione) antiserum with its specific antigen and other chemicals with very low cross-reactivity coefficients was studied by means of Raman spectroscopy. The experimental results indicate that the predominant secondary structure of this antiserum is the bsheet conformation and that the interaction with the ligands is able to modify the overall structure of the protein. The antiserum-antigen binding causes a slight decrease in the random conformation in all systems, whereas the changes in the b-sheet and a-helix content depend on the nature of the ligands. Ligands with a high cross-reactivity coefficient increase the a-helix percentage, whereas the opposite effect is observed with low cross-reactivity ligands. The stereochemical properties of the substituents in the 5-position of the heterocyclic ring, relative to the rest of the molecule, are an important factor in determining the crossreactivity and the kind of interaction with the antiserum. If in this position only one phenyl group is present, the antiserum-ligand affinity is low and the a-helix percentage decreases, but when in this position two phenyl groups are present, the affinity is high and the a-helix percentage increases. As regards the tertiary structure of the antiserum protein, alkyl side-chains and Trp residues contribute to the stability of the antiserum-specific antigen complex by means of hydrophobic interactions. The spectral features of alkyl side-chains and Trp do not change in the presence of ligands with low affinity.
Drug-Antiserum molecular interactions a Raman spectroscopic study
A Torreggiani;
1999
Abstract
The binding of the phenytoin (5,5-diphenyl-2,4-imidazolidinedione) antiserum with its specific antigen and other chemicals with very low cross-reactivity coefficients was studied by means of Raman spectroscopy. The experimental results indicate that the predominant secondary structure of this antiserum is the bsheet conformation and that the interaction with the ligands is able to modify the overall structure of the protein. The antiserum-antigen binding causes a slight decrease in the random conformation in all systems, whereas the changes in the b-sheet and a-helix content depend on the nature of the ligands. Ligands with a high cross-reactivity coefficient increase the a-helix percentage, whereas the opposite effect is observed with low cross-reactivity ligands. The stereochemical properties of the substituents in the 5-position of the heterocyclic ring, relative to the rest of the molecule, are an important factor in determining the crossreactivity and the kind of interaction with the antiserum. If in this position only one phenyl group is present, the antiserum-ligand affinity is low and the a-helix percentage decreases, but when in this position two phenyl groups are present, the affinity is high and the a-helix percentage increases. As regards the tertiary structure of the antiserum protein, alkyl side-chains and Trp residues contribute to the stability of the antiserum-specific antigen complex by means of hydrophobic interactions. The spectral features of alkyl side-chains and Trp do not change in the presence of ligands with low affinity.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
