Strategies and opportunities for engineering antifungal peptides for therapeutic applications

Konakbayeva, Dinara; Karlsson, Amy J.

doi:10.1016/j.copbio.2023.102926

Cited by 12 publications

(4 citation statements)

References 56 publications

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“…Antimicrobial peptides (AMPs) produced by living organisms attract particular interest as new antimicrobial agents with their wide range of biotargets (bacteria, fungi, parasites) capable of replacing blockbuster antibiotics [21]. To date, there are a number of databases for documenting AMPs [22].…”

Section: Antifungal Peptides (Afps)mentioning

confidence: 99%

Various Biomimetics, Including Peptides as Antifungals

Efremenko,

Aslanli,

Stepanov

et al. 2023

Biomimetics

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Biomimetics, which are similar to natural compounds that play an important role in the metabolism, manifestation of functional activity and reproduction of various fungi, have a pronounced attraction in the current search for new effective antifungals. Actual trends in the development of this area of research indicate that unnatural amino acids can be used as such biomimetics, including those containing halogen atoms; compounds similar to nitrogenous bases embedded in the nucleic acids synthesized by fungi; peptides imitating fungal analogs; molecules similar to natural substrates of numerous fungal enzymes and quorum-sensing signaling molecules of fungi and yeast, etc. Most parts of this review are devoted to the analysis of semi-synthetic and synthetic antifungal peptides and their targets of action. This review is aimed at combining and systematizing the current scientific information accumulating in this area of research, developing various antifungals with an assessment of the effectiveness of the created biomimetics and the possibility of combining them with other antimicrobial substances to reduce cell resistance and improve antifungal effects.

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Section: Antifungal Peptides (Afps)mentioning

confidence: 99%

Various Biomimetics, Including Peptides as Antifungals

Efremenko,

Aslanli,

Stepanov

et al. 2023

Biomimetics

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show abstract

“…Antimicrobial peptides (AMPs) produced by living organisms attract particular interest as new antimicrobial agents with a wide range of biotargets (bacteria, fungi, parasites) capable of replacing blockbuster antibiotics [20]. To date, there are a number of databases for documenting AMPs [21].…”

Section: Antifungal Peptides (Afps)mentioning

confidence: 99%

Various Biomimetics as Antifungals

Efremenko,

Aslanli,

Stepanov

et al. 2023

Preprint

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Biomimetics, which are similar to natural compounds that play an important role in the metabolism, manifestation of functional activity and reproduction of various fungi, have a pronounced attrac-tion in the current search for new effective antifungals. Actual trends in the development of this area of research indicate that unnatural amino acids can be used as such biomimetics, including those containing halogen atoms; compounds similar to nitrogenous bases embedded in the nucleic acids synthesized by fungi; peptides imitating fungal analogues; molecules similar to natural sub-strates of numerous fungal enzymes and Quorum Sensing signaling molecules of fungi and yeast; etc. Most part of the review is devoted to the analysis of semi-synthetic and synthetic antifungal peptides and their targets of action. This review is aimed at combining and systematizing the cur-rent scientific information accumulating in this area of research, developing various antifungals with an assessment of the effectiveness of the created biomimetics and the possibility of combining them with other antimicrobial substances to reduce cell resistance and improve antifungal effects.

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“…Systemic use of peptides has been an essential barrier to commercialization, especially because peptides are susceptible to proteolytic degradation, and interactions with ions and salt present in body fluids decrease the activity of AFPs and shorten their half-lives [ 118 , 119 ]. Among the challenges of using AMPs are the possible loss of microbicidal activity of these molecules in the presence of biological concentrations of cations (Na + , Mg 2,+ and Ca 2+ ); it is proposed that, in certain situations, the immunomodulatory properties of the peptides are as essential as the antimicrobial activity in fighting infections in vivo [ 120 ].…”

Section: Antimicrobial Peptides (Amps)mentioning

confidence: 99%

“…Human proteases and those produced by fungal pathogens are important in this process of AFP inactivation, e.g., C. albicans secreted aspartic proteases which can inactivate histatin-5 [ 123 , 124 ]. Another challenge is toxicity, once AFPs need to be selective toward fungal cells over mammalian cells, and those with pore formation as a mechanism of action can be nonspecific once fungal and mammalian membranes are similar [ 119 , 125 ].…”

Section: Antimicrobial Peptides (Amps)mentioning

confidence: 99%

Candida albicans and Antifungal Peptides

Freitas,

Felipe

2023

Infect Dis Ther

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Candida albicans , a ubiquitous opportunistic fungal pathogen, plays a pivotal role in human health and disease. As a commensal organism, it normally resides harmlessly within the human microbiota. However, under certain conditions, C. albicans can transition into a pathogenic state, leading to various infections collectively known as candidiasis. With the increasing prevalence of immunocompromised individuals and the widespread use of invasive medical procedures, candidiasis has become a significant public health concern. The emergence of drug-resistant strains further complicates treatment options, highlighting the urgent need for alternative therapeutic strategies. Antifungal peptides (AFPs) have gained considerable attention as potential candidates for combating Candida spp. infections. These naturally occurring peptides possess broad-spectrum antimicrobial activity, including specific efficacy against C. albicans . AFPs exhibit several advantageous properties, such as rapid killing kinetics, low propensity for resistance development, and diverse mechanisms of action, making them promising alternatives to conventional antifungal agents. In recent years, extensive research has focused on discovering and developing novel AFPs with improved efficacy and selectivity against Candida species. Advances in biotechnology and synthetic peptide design have enabled the modification and optimization of natural peptides, enhancing their stability, bioavailability, and therapeutic potential. Nevertheless, several challenges must be addressed before AFPs can be widely implemented in clinical practice. These include optimizing peptide stability, enhancing delivery methods, overcoming potential toxicity concerns, and conducting comprehensive preclinical and clinical studies. This commentary presents a short overview of candidemia and AFP; articles and reviews published in the last 10 years were searched on The National Library of Medicine (National Center for Biotechnology Information–NIH–PubMed). The terms used were C. albicans infections, antimicrobial peptides, antifungal peptides, antifungal peptides mechanisms of action, candidemia treatments and guidelines, synthetic peptides and their challenges, and antimicrobial peptides in clinical trials as the main ones. Older publications were cited if they brought some relevant concept or helped to bring a perspective into our narrative. Articles older than 20 years and those that appeared in PubMed but did not match our goal to bring updated information about using antifungal peptides as an alternative to C. albicans infections were not considered.

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Strategies and opportunities for engineering antifungal peptides for therapeutic applications

Cited by 12 publications

References 56 publications

Various Biomimetics, Including Peptides as Antifungals

Various Biomimetics, Including Peptides as Antifungals

Various Biomimetics as Antifungals

Candida albicans and Antifungal Peptides

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