Analogs and conjugates of natural proline-arginine-rich antimicrobial peptides: their potential for practical applications

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Abstract

Antimicrobial peptides, particularly proline-arginine-rich cationic antimicrobial peptides (PRAMPs), have recently attracted the attention of researchers as potential candidates for the development of new generation antibacterial drugs. This interest stems from PRAMPs’ ability to target bacteria resistant to currently used antibiotics, through a unique mechanism involving interaction with bacterial ribosomes and inhibition of protein synthesis. Additionally, PRAMPs exhibit a broad spectrum of activity against Gram-negative bacteria, low rates of bacterial resistance, and relative ease of structural modification. The use of antimicrobial peptides in practice is limited due to several factors, including their susceptibility to proteolytic degradation in biological media and their insufficiently broad spectrum of antibacterial activity against Gram-positive bacteria. Additionally, there is a possibility of resistance developing in bacteria against AMPs, as well as toxic effects resulting from the interaction of PRAMPs with certain components of eukaryotic cells. To overcome these challenges, researchers have explored various strategies, such as modifying the structure of PRAMPs and conjugating them with other molecules. This review examines recent literature on analogues and conjugates of PRAMPs, along with information on methods of modifying PRAMPs. The analysis of new properties of these compounds highlights the potential for creating effective antibacterial agents based on PRAMPs.

About the authors

P. R. Bazhutov

Lomonosov Moscow State University, Department of Chemistry

Moscow, 119991 Russia

Z. Z. Khairullina

Lomonosov Moscow State University, Department of Chemistry

Moscow, 119991 Russia

A. G. Tereshchenkov

Lomonosov Moscow State University, Department of Chemistry; Lomonosov Moscow State University, A.N. Belozersky Institute of Physico-Chemical Biology

Moscow, 119991 Russia; Moscow, 119992 Russia

N. V. Sumbatyan

Lomonosov Moscow State University, Department of Chemistry

Email: sumbtyan@belozersky.msu.ru
Moscow, 119991 Russia

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