Key Physicochemical Determinants in the Antimicrobial Peptide RiLK1 Promote Amphipathic Structures

Falcigno, Lucia; D’Auria, Gabriella; Palmieri, Gianna; Gogliettino, Marta; Agrillo, Bruna; Tatè, Rosarita; Dardano, Principia; Nicolais, L.; Balestrieri, Marco

doi:10.3390/ijms221810011

Cited by 8 publications

(10 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our previous studies, the structural characterization as well as the antibacterial and antifungal activities of the peptides 1018-K6, MTP1, RiLK1, and RiLK3 were demonstrated [42][43][44][45][46], thus leading to investigations of their possible antiviral effects that have not been studied so far, considering that the ultimate goal of research is to find agents that exhibit a broad-spectrum antimicrobial activity and are therefore attractive for manufacturing applications. Moreover, two further peptides were considered in our study to expand the panel of potential antiviral compounds (Table 1), the newly designed RiLK30 and the already-known HIV inhibitor AVP2 [47], which was used as a reference.…”

Section: Peptide Designmentioning

confidence: 99%

“…We have recently demonstrated the antibacterial activity of a panel of designed AMPs against food pathogen contaminants, including Gram-positive and Gram-negative bacteria and fungi but not viruses [42][43][44][45][46]. The structural properties and mechanism of action of these peptides have been elucidated previously and these compounds were also found to be non-cytotoxic [42][43][44][45][46].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Reliable Multifaceted Solution against Foodborne Viral Infections: The Case of RiLK1 Decapeptide

Galatola,

Agrillo,

Gogliettino

et al. 2024

Preprint

View full text Add to dashboard Cite

Food-borne transmission is a recognized route for many viruses associated with gastrointestinal, hepatic or neurological diseases. Therefore, it is essential to identify new bioactive compounds with broad-spectrum antiviral activity is needed to exploit innovative solutions against these hazards. Lately, antimicrobial peptides (AMPs) have been recognized as promising antiviral agents. Indeed, while the antibacterial and antifungal effects of these molecules have been widely reported, their use as potential antiviral agents has not yet been fully investigated. Herein, the antiviral activity of previously identified or newly designed AMPs, was evaluated against the non-enveloped RNA viruses, Hepatitis A virus (HAV), and Murine Norovirus (MNV), a surrogate for human Norovirus. Moreover, specific assays were performed to recognize at which stage of the viral infection cycle the peptides could function. Results showed that almost all peptides displayed virucidal effects with about 90% of infectivity reduction on HAV or MNV. However, the decapeptide RiLK1 demonstrated, together with its antibacterial and antifungal properties, a notable reduction in viral infection for both HAV and MNV, possibly through direct interaction with viral particles or inhibition of the viral bonding to the cell receptors. Hence, RiLK1 could represent a versatile ‘antimicrobial agent effective against various foodborne pathogens including viruses, bacteria, and fungi.

show abstract

Section: Peptide Designmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Reliable Multifaceted Solution against Foodborne Viral Infections: The Case of RiLK1 Decapeptide

Galatola,

Agrillo,

Gogliettino

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Recently, a new 10-amino acid peptide, namely RiLK1 ( Agrillo et al, 2020 ; Falcigno et al, 2021 ), was designed based on the dodecapeptide 1018-K6 ( Palmieri et al, 2018 ; Colagiorgi et al, 2020 ; Festa et al, 2021 ; Ambrosio et al, 2022 ), a compound derived from a bovine HDP (host defence peptide) bactenecin, belonging to the cathelicidins family. Structural and functional analysis, revealed that RiLK1 is extremely active toward fungi, viruses, Gram-positive and-negative bacteria at low micromolar concentrations, showing no effects on human cell lines investigated in terms of viability and morphology.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial activity, membrane interaction and structural features of short arginine-rich antimicrobial peptides

Agrillo,

Porritiello,

Gratino

et al. 2023

Front. Microbiol.

Self Cite

View full text Add to dashboard Cite

Antimicrobial activity of many AMPs can be improved by lysine-to-arginine substitution due to a more favourable interaction of arginine guanidinium moiety with bacterial membranes. In a previous work, the structural and functional characterization of an amphipathic antimicrobial peptide named RiLK1, including lysine and arginine as the positively charged amino acids in its sequence, was reported. Specifically, RiLK1 retained its β-sheet structure under a wide range of environmental conditions (temperature, pH, and ionic strength), and exhibited bactericidal activity against Gram-positive and Gram-negative bacteria and fungal pathogens with no evidence of toxicity on mammalian cells. To further elucidate the influence of a lysine-to-arginine replacement on RiLK1 conformational properties, antimicrobial activity and peptide-liposome interaction, a new RiLK1-derivative, named RiLK3, in which the lysine is replaced with an arginine residue, was projected and characterised in comparison with its parental compound. The results evidenced that lysine-to-arginine mutation not only did not assure an improvement in the antimicrobial potency of RiLK1 in terms of bactericidal, virucidal and fungicidal activities, but rather it was completely abolished against the hepatitis A virus. Therefore, RiLK1 exhibited a wide range of antimicrobial activity like other cationic peptides, although the exact mechanisms of action are not completely understood. Moreover, tryptophan fluorescence measurements confirmed that RiLK3 bound to negatively charged lipid vesicles with an affinity lower than that of RiLK1, although no substantial differences from the structural and self-assembled point of view were evidenced. Therefore, our findings imply that antimicrobial efficacy and selectivity are affected by several complex and interrelated factors related to substitution of lysine with arginine, such as their relative proportion and position. In this context, this study could provide a better rationalisation for the optimization of antimicrobial peptide sequences, paving the way for the development of novel AMPs with broad applications.

show abstract

“…Cationic amino acids (lysine/arginine) provide the initial electrostatic interaction with the negatively charged membrane surfaces of the microbes [ 16 ]. Aromatic residues such as phenylalanine and tryptophan play important roles in antimicrobial and hemolytic activities as they facilitate the formation of amphipathic structures and are fundamental for the interaction at the interface between the aqueous solution and the hydrophobic membrane bilayer [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Synthetic Amphipathic β-Sheet Temporin-Derived Peptide with Dual Antibacterial and Anti-Inflammatory Activities

et al. 2022

View full text Add to dashboard Cite

Temporin family is one of the largest among antimicrobial peptides (AMPs), which act mainly by penetrating and disrupting the bacterial membranes. To further understand the relationship between the physical-chemical properties and their antimicrobial activity and selectivity, an analogue of Temporin L, [Nle1, DLeu9, DLys10]TL (Nle-Phe-Val-Pro-Trp-Phe-Lys-Phe-dLeu-dLys-Arg-Ile-Leu-CONH2) has been developed in the present work. The design strategy consisted of the addition of a norleucine residue at the N-terminus of the lead peptide sequence, [dLeu9, dLys10]TL, previously developed by our group. This modification promoted an increase of peptide hydrophobicity and, interestingly, more efficient activity against both Gram-positive and Gram-negative strains, without affecting human keratinocytes and red blood cells survival compared to the lead peptide. Thus, this novel compound was subjected to biophysical studies, which showed that the peptide [Nle1, dLeu9, dLys10]TL is unstructured in water, while it adopts β-type conformation in liposomes mimicking bacterial membranes, in contrast to its lead peptide forming α-helical aggregates. After its aggregation in the bacterial membrane, [Nle1, dLeu9, dLys10]TL induced membrane destabilization and deformation. In addition, the increase of peptide hydrophobicity did not cause a loss of anti-inflammatory activity of the peptide [Nle1, dLeu9, dLys10]TL in comparison with its lead peptide. In this study, our results demonstrated that positive net charge, optimum hydrophobic−hydrophilic balance, and chain length remain the most important parameters to be addressed while designing small cationic AMPs.

show abstract

Key Physicochemical Determinants in the Antimicrobial Peptide RiLK1 Promote Amphipathic Structures

Cited by 8 publications

References 62 publications

A Reliable Multifaceted Solution against Foodborne Viral Infections: The Case of RiLK1 Decapeptide

A Reliable Multifaceted Solution against Foodborne Viral Infections: The Case of RiLK1 Decapeptide

Antimicrobial activity, membrane interaction and structural features of short arginine-rich antimicrobial peptides

Synthetic Amphipathic β-Sheet Temporin-Derived Peptide with Dual Antibacterial and Anti-Inflammatory Activities

Contact Info

Product

Resources

About