Pillar[5]arene/albumin biosupramolecular systems for simultaneous native protein preservation and encapsulation of a water-soluble substrate

The growing resistance of pathogens, bacteria, viruses, and fungi to a number of drugs has encouraged researchers to use natural and synthetic biomimetic systems to overcome this challenge. Multicomponent systems are an attractive approach for drug design and multitarget therapy. In this study, we report the assembly of a three-component (pillar[5]arene, bovine serum albumin, and methyl orange) biosupramolecular system as a potential drug delivery system. We estimated the cytotoxic activity and transfection ability of pillar[5]arene derivatives and investigated the effect of the nature of macrocycle functions (l-phenylalanine, glycine, l-alanine) on the native conformation of serum albumin in a three-component system. NMR, UV-vis, fluorescence, CD spectroscopy, DLS, and molecular docking studies were performed in order to confirm the structure and possible pillar[5]arene/bovine serum albumin/methyl orange interactions occurring during the association process. Results indicate that pillar[5]arene with l-phenylalanine fragments retains the native form of BSA to the maximum extent and forms more stable associates. Pillar[5]arene with l-phenylalanine fragments retains the native form of BSA. Betaine pillar[5]arenes recognize the specific pocket of serum albumin.