Natural and synthetic peptides in antimicrobial therapy

Abstract

Antimicrobial function of innate immunity is mediated by the low-molecular weight peptides which are active against bacteria, fungi and some viruses. The review presents data on studies of both natural and synthetic peptides regarding the features of their structure and therapeutic effect. As a rule, the molecules of such peptides are positively charged, due to amino acid radicals capable of protonation. Spatially, antimicrobial peptide molecules are arranged as -helices or -layers in separate or compound assemblies. At the same time, short molecular chains, including up to 18 amino acid residues, exist as a linear or cyclic forms, remaining at the level of primary spatial structure. Natural antimicrobial peptides are predominantly produced by neutrophilic granulocytes and macrophages, as well as epithelial cells of the barrier organs. Three families of natural antimicrobial peptides have been most studied: defensins, cathelicidins, and histatins. Defensins are active against Gram-positive and Gram-negative bacteria, viruses and fungi, having anti-inflammatory and immunomodulatory activity. Cathelicidins are chemoattractants and exert antibacterial, immunomodulatory, wound healing, antitumor effects, potentially contributing to the development of autoimmune diseases. Histatins have a pronounced fungicidal effect and prevent the formation of bacterial biofilms. A detailed study on the structure and principles of action of natural antimicrobial peptides made it possible to apply this information for the in vitro synthesis of peptides thus making it possible to create multipurpose drugs based on them. E.g., synthetic peptides WR12 and D-IK8 ensure the delivery of antibiotics to infected or tumor cells, due to permeabilization of cellular membranes. At the same time, a synthetic peptide, acipensin 1, is capable of penetrating into human tumor cells without damaging them. The immunomodulatory peptide glutoxim is effectively used in anti-tuberculosis therapy. ZP2 peptide, the functional site of granulocyte-macrophage colony-stimulating factor is effective against Gram-negative bacteria (K. pneumoniae, P. aeruginosa and A. baumannii) as well as EpsteinBarr virus. Thymic immunoregulatory peptides bestim, hepon, thymogen and imunofan are inducers of endogenous - and -interferon production, inhibit the development of malignant neoplasms, and possess anti-inflammatory activity. Gepon is used in the treatment of viral hepatitis, respiratory and opportunistic infections, croup syndrome and sexually transmitted infections (including genital herpes). Thus, the synthetic antimicrobial peptides are widely used in complex treatment regimens along with conventional antibiotics, antiviral, and antitumor drugs, thus making it possible to achieve higher therapeutic effect.