Probing the interactions of dansyl appended sequence-defined oligomers with serum albumins: Effect of functionality, hydrophobicity, and architecture

Abstract

In this work, a library of functionally and structurally tuneable macromolecules were synthesised and their interaction with serum proteins were studied experimentally and theoretically, with an aim to identify the driving factors that influence protein-drug interaction. The parameters taken for assessment were (a) the number and type of functional groups (dithiocarbamate, ester and amide) present in the backbone and sidechain, (b) different architectures including linear and branched, and (c) hydrophobic/hydrophilic character. Dansyl moiety was attached to make these macromolecules a suitable acceptor for FRET with serum proteins. The binding constant values calculated from the fluorescence titrations indicated that an optimum hydrophobic character, chain length and architecture are essential for a favourable interaction with BSA/HSA. By changing the above mentioned three factors, we were able to achieve a wide range of binding constant values in the range of (2.99–7.91) × 104 M−1 for BSA and (1.64–11.7) × 104 M−1 for HSA. The number of binding sites varied from 1.13 to 1.69 for BSA and 0.89 to 1.35 for HSA. Also, the energy transfer efficiency was calculated and it falls in the range of 63.9–88.7% and 52.0–84.2% respectively for BSA and HSA. The quenching mechanism for serum protein-drug complex was found to involve both static and dynamic quenching. Moreover, this structure–activity relationship was also backed by molecular docking studies.