A Spectral Approach to Study Interaction between Chitosan Modified with Mannose and Concavalin A for the Creation of Add
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ectral Approach to Study Interaction between Chitosan Modified with Mannose and Concavalin A for the Creation of Address Delivery Systems of Antituberculosis Drugs I. M. Le-Deygena, *, P. V. Mamaevaa, A. A. Skuredinaa, and E. V. Kudryashovaa aDepartment
of Chemistry, Moscow State University, Moscow, Russia *e-mail: [email protected]
Received January 10, 2020; revised January 12, 2020; accepted January 20, 2020
Abstract—We present a comprehensive study of the receptor–ligand interaction by spectral methods on the example of Concanavalin A lectin and 5 kDa chitosan modified with D-mannose. An improved method for the modification of chitosan with D-mannose and purification of these conjugates is developed. A novel approach to calculate the constants of the Concavalin A binding with the mannose-containing ligand is proposed. The calculation is based on the intensity reduction of the Amide II absorption band in the IR spectra normalized by Amide I during the receptor binding with the modified chitosan-mannose polymer. The linearization of the binding curves in Scatchard coordinates allows finding the complex dissociation constants whose value constituted (5.5 ± 0.3) × 10–5 M. These results are confirmed by fluorescence polarization analysis. IR spectroscopy is found to be the most suitable and precise method for the calculation of dissociation constants, which does not require preliminary protein modification. Keywords: lectins, ligand–receptor interaction, chitosan, FTIR DOI: 10.3103/S0027131420040045
Tuberculosis is one of the most dangerous infections in both developing and developed countries. Long-term therapy by high doses of antibiotics leads to side effects that harm the patient’s quality of life and facilitate the appearance of multiresistant M. tuberculosis strains. A wide range of delivery systems for antituberculosis drugs (ATDs), composed of liposomal [1], oligosaccharide [2], and polymeric [3] systems, are known. However, the majority of nano- and submicron particles do not sufficiently efficiently reach their targets in the treatment of pulmonary tuberculosis. Therefore, better targeting of delivery systems to alveolar macrophages, which are infected by M. tuberculosis, is required [4]. The synthesis of biocompatible polymers for the creation of drug delivery systems with the effect of active targeting is an important task in biomedical chemistry. D-mannose and its derivatives are promising because the corresponding receptors are actively expressed on the surface of alveolar macrophages [5, 6]. Similar molecules can be used to create both polymeric and liposomal ATD delivery systems. Chitosan (natural aminopolysaccharide) represents a promising polymer for the creation of an Abbreviations: ATDs, antituberculosis drugs; ConA, Concanavalin A; TNBSA, trinitrobenzenesulfonic acid; PBS, phosphate buffered saline; FITC, fluorescein isothiocyanate.
ATD delivery system due to its mucoadhesive properties and biocompatibility. Many amino groups available for interaction enable a broad range of modification re
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