Can simple UV-Vis measurements with tryptophan serve as a screening model for potential drug-AGP interactions?

Alpha-1-acid glycoprotein (AGP) is a key plasma protein involved in the binding and transport of numerous drugs, particularly basic compounds. The aim of this study was to evaluate whether simple UV-Vis measurements using tryptophan as a model component of the AGP binding site could serve as a screening method for assessing potential drug-AGP binding interactions. Thirty drugs with diverse chemical structures were analyzed. UV-Vis spectra were recorded for the drug alone, tryptophan alone, and the drug-tryptophan mixture and the experimental mixture spectra were compared with theoretical additive spectra. A series of parameters describing deviations from additivity, including U, RB, RW, L+W − L and L+W − Add were calculated and subjected to statistical analysis.

The parameters U, RB and RW consistently identified the same group of 12 drugs showing evidence of interaction with tryptophan. Paroxetine represented a borderline interaction, suggesting a weaker effect than that observed for the remaining compounds. Relationships were also observed between the spectrophotometric parameters and selected physicochemical descriptors, particularly polar surface area and the HOMO–LUMO energy gap. Multiple and logistic regression analyses indicated that selected physicochemical properties contributed to the differentiation between interacting and non-interacting compounds. Overall, the results suggest that UV-Vis measurements with tryptophan may provide a simple screening approach for the preliminary assessment of potential drug-AGP binding interactions, particularly when combined with physicochemical and chromatographic descriptors.