THETA-DEFENSINS: QUANTUM-CHEMICAL ANALYSIS OF PROBABLE MECHANISMS OF INTERACTION WITH MEMBRANES OF MICROORGANISMS

Abstract

Theta -defensins are the only cyclic antibiotic peptides produced in the mammalian body. Theta -defensins are active against archaea, bacteria, fungi, protozoa, some viruses and even toxins, and these properties are inherent to the cyclic form of their molecule. The production of defensins represents one of the mechanisms of innate immunity, i.e. it is part of the first line of defense of the macroorganism. In this article, we present the analysis of quantum -chemical calculation of the geometry, electron density distribution and hydrophobicity parameters of the theta -defensin molecule, describe its physical and chemical properties and from these positions we consider the probable mechanisms of its interaction with the membranes of microorganisms. The transverse diameter of the theta -defensin molecule allows it to penetrate into the pores formed by porins in the bacterial membrane. Three disulfide bridges give the theta -defensin molecule rigidity. The distances between these bridges are such that they allow both free and hydrated biogenic ions to pass through the voids they form (and, possibly, through the bacterial wall into which the theta -defensin molecule has embedded), which should lead to the destruction of the bacteria. The theta -defensin molecule has a very high dipole moment. This increases the intensity of the dipole -dipole interaction between the theta -defensin molecules, increases their affinity to each other and can lead to the formation of complexes of these molecules - In a chain or, less likely, staircase type. Theta -defensins are promising as medicinal antimicrobial agents.