Optimizing Antimicrobial Peptide Design: Integration of Cell-Penetrating Peptides, Amyloidogenic Fragments, and Amino Acid Residue Modifications.

The escalating threat of multidrug-resistant pathogens necessitates innovative approaches to combat infectious diseases. In this study, we examined peptides R23F*, V31K*, and R44K*, which were engineered to include an amyloidogenic fragment sourced from the S1 protein of , along with one or two cell-penetrating peptide (CPP) components. We assessed the antimicrobial efficacy of these peptides in a liquid medium against various strains of both Gram-positive bacteria, including (209P and 129B strains), MRSA (SA 180 and ATCC 43300 strains), and (strain IP 5832), and Gram-negative bacteria such as (ATCC 28753 and 2943 strains) and (MG1655 and K12 strains).

Enhancing the Antimicrobial Properties of Peptides through Cell-Penetrating Peptide Conjugation: A Comprehensive Assessment.

Combining antimicrobial peptides (AMPs) with cell-penetrating peptides (CPPs) has shown promise in boosting antimicrobial potency, especially against Gram-negative bacteria. We examined the CPP-AMP interaction with distinct bacterial types based on cell wall differences. Our investigation focused on AMPs incorporating penetratin CPP and dihybrid peptides containing both cell-penetrating TAT protein fragments from the human immunodeficiency virus and Antennapedia peptide (Antp).

The Strategies of Development of New Non-Toxic Inhibitors of Amyloid Formation.

In recent years, due to the aging of the population and the development of diagnostic medicine, the number of identified diseases associated with the accumulation of amyloid proteins has increased. Some of these proteins are known to cause a number of degenerative diseases in humans, such as amyloid-beta (Aβ) in Alzheimer's disease (AD), α-synuclein in Parkinson's disease (PD), and insulin and its analogues in insulin-derived amyloidosis. In this regard, it is important to develop strategies for the search and development of effective inhibitors of amyloid formation.

The Increased Amyloidogenicity of Spike RBD and pH-Dependent Binding to ACE2 May Contribute to the Transmissibility and Pathogenic Properties of SARS-CoV-2 Omicron as Suggested by In Silico Study.

SARS-CoV-2 is a rapidly evolving pathogen that has caused a global pandemic characterized by several consecutive waves. Based on epidemiological and NGS data, many different variants of SARS-CoV-2 were described and characterized since the original variant emerged in Wuhan in 2019. Notably, SARS-CoV-2 variants differ in transmissibility and pathogenicity in the human population, although the molecular basis for this difference is still debatable.

Amyloidogenic Peptides: New Class of Antimicrobial Peptides with the Novel Mechanism of Activity.

Antibiotic-resistant bacteria are recognized as one of the leading causes of death in the world. We proposed and successfully tested peptides with a new mechanism of antimicrobial action "protein silencing" based on directed co-aggregation. The amyloidogenic antimicrobial peptide (AAMP) interacts with the target protein of model or pathogenic bacteria and forms aggregates, thereby knocking out the protein from its working condition.

Multiple Antimicrobial Effects of Hybrid Peptides Synthesized Based on the Sequence of Ribosomal S1 Protein from .

The need to develop new antimicrobial peptides is due to the high resistance of pathogenic bacteria to traditional antibiotics now and in the future. The creation of synthetic peptide constructs is a common and successful approach to the development of new antimicrobial peptides. In this work, we use a simple, flexible, and scalable technique to create hybrid antimicrobial peptides containing amyloidogenic regions of the ribosomal S1 protein from .

Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of ?

The development and testing of new antimicrobial peptides (AMPs) represent an important milestone toward the development of new antimicrobial drugs that can inhibit the growth of pathogens and multidrug-resistant microorganisms such as Gram-negative bacteria. Most AMPs achieve these goals through mechanisms that disrupt the normal permeability of the cell membrane, which ultimately leads to the death of the pathogenic cell. Here, we developed a unique combination of a membrane penetrating peptide and peptides prone to amyloidogenesis to create hybrid peptide: "cell penetrating peptide + linker + amyloidogenic peptide".

Identification of Amyloidogenic Regions in Ribosomal S1 Protein.

Bacterial S1 protein is a functionally important ribosomal protein. It is a part of the 30S ribosomal subunit and is also able to interact with mRNA and tmRNA. An important feature of the S1 protein family is a strong tendency towards aggregation.

Antimicrobial and Amyloidogenic Activity of Peptides. Can Antimicrobial Peptides Be Used against SARS-CoV-2?

At present, much attention is paid to the use of antimicrobial peptides (AMPs) of natural and artificial origin to combat pathogens. AMPs have several points that determine their biological activity. We analyzed the structural properties of AMPs, as well as described their mechanism of action and impact on pathogenic bacteria and viruses.

New Model for Stacking Monomers in Filamentous Actin from Skeletal Muscles of .

To date, some scientific evidence (limited proteolysis, mass spectrometry analysis, electron microscopy (EM)) has accumulated, which indicates that the generally accepted model of double-stranded of filamentous actin (F-actin) organization in eukaryotic cells is not the only one. This entails an ambiguous understanding of many of the key cellular processes in which F-actin is involved. For a detailed understanding of the mechanism of F-actin assembly and actin interaction with its partners, it is necessary to take into account the polymorphism of the structural organization of F-actin at the molecular level.

Antimicrobial and Amyloidogenic Activity of Peptides Synthesized on the Basis of the Ribosomal S1 Protein from Thermus Thermophilus.

Controlling the aggregation of vital bacterial proteins could be one of the new research directions and form the basis for the search and development of antibacterial drugs with targeted action. Such approach may be considered as an alternative one to antibiotics. Amyloidogenic regions can, like antibacterial peptides, interact with the "parent" protein, for example, ribosomal S1 protein (specific only for bacteria), and interfere with its functioning.

Amyloidogenic Propensities of Ribosomal S1 Proteins: Bioinformatics Screening and Experimental Checking.

Structural S1 domains belong to the superfamily of oligosaccharide/oligonucleotide-binding fold domains, which are highly conserved from prokaryotes to higher eukaryotes and able to function in RNA binding. An important feature of this family is the presence of several copies of the structural domain, the number of which is determined in a strictly limited range from one to six. Despite the strong tendency for the aggregation of several amyloidogenic regions in the family of the ribosomal S1 proteins, their fibril formation process is still poorly understood.

Determination of amyloid core regions of insulin analogues fibrils.

Unlabelled: A rapid-acting insulin lispro and long-acting insulin glargine are commonly used for the treatment of diabetes. Clinical cases have described the formation of injectable amyloidosis with these insulin analogues, but their amyloid core regions of fibrils were unknown. To reveal these regions, we have analysed the hydrolyzates of insulin fibrils and its analogues using high-performance liquid chromatography and mass spectrometry methods and found that insulin and its analogues have almost identical amyloid core regions that intersect with the predicted amyloidogenic regions.