Structure and Location of Protein Sites Binding Self-Associated Congo Red Molecules with Intercalated Drugs as Compact Ligands-Theoretical Studies.

Roterman Irena,Kwiecińska Klaudia,Ptak-Kaczor Magdalena,Korchowiec Jacek,Jagusiak Anna,Banach Mateusz,Chłopaś Katarzyna

doi:10.3390/biom11040501

Abstract

In the search for new carriers capable of transporting toxic drugs to a target, particular attention has been devoted to supramolecular systems with a ribbon-like micellar structure of which Congo red is an example. A special promise of the possible use of such systems for directing drugs to a target emerges from their particular affinity to immune complexes and as an independent property, binding many organic compounds including drugs by intercalation. Serum albumin also appeared able to bind micellar particles of such systems. It may protect them against dilution in transport. The mathematical tool, which relies on analysis of the distribution of polarity and hydrophobicity in protein molecules (fuzzy oil drop model), has been used to find the location of binding area in albumin as well as anchorage site for Congo red in heated IgG light chain used as a model presenting immunoglobulin-like structures. Results confirm the suggested formerly binding site of Congo red in V domain of IgG light chain and indicated the cleft between pseudo-symmetric domains of albumin as the area of attachment for the dye.

Highlights

Therapies that rely on highly toxic drugs such as Doxorubicin (Dox), often applied in cancer treatment, are a double-edged sword
The first part discusses albumin, both as a complete molecule and with regard to individual domains, while the second part will be devoted to the IgG light chain, with particular focus on its V domain
Capacity for Binding Congo Red in Complex with Dox Based on the Fuzzy Oil Drop Model

Summary

Introduction

Therapies that rely on highly toxic drugs such as Doxorubicin (Dox), often applied in cancer treatment, are a double-edged sword. The drug does preferentially destroy cancer cells due to their increased susceptibility caused by frequent division, but its deleterious influence on other tissues ( bone marrow) is well understood, the concerns about its toxicity. One possible solution to this dilemma would be to ensure that the drug acts only upon its intended target, limiting any potential side effects. Many attempts have been made to bring about such an outcome. One of them includes administering the drug in complex with a carrier, limiting its toxic effects and enabling rapid elimination of surplus drug molecules. Supramolecular systems— those which form ribbonlike micelles (of which Congo red is an example)—are a promising lead in this respect [1]

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