Designed Multifunctional Peptides for Intracellular Targets

Juretić, Davor

doi:10.3390/antibiotics11091196

Cited by 11 publications

(9 citation statements)

References 320 publications

(479 reference statements)

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“…However, it was placed between green and pink communities containing members such as Pac-525, WLBU2, Indolicidin and protegrin-1, whose mode of action is closely related to that reported for TetraF2W-RR (bacterial membrane disruption). These four ABFPs are arginine ®-rich peptides containing repeated units of R, allowing interaction with negatively-charged bacterial membranes, the formation of transmembrane pores, and cell penetration [ 70 ].…”

Section: Resultsmentioning

confidence: 99%

Complex Networks Analyses of Antibiofilm Peptides: An Emerging Tool for Next-Generation Antimicrobials’ Discovery

et al. 2023

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Microbial biofilms cause several environmental and industrial issues, even affecting human health. Although they have long represented a threat due to their resistance to antibiotics, there are currently no approved antibiofilm agents for clinical treatments. The multi-functionality of antimicrobial peptides (AMPs), including their antibiofilm activity and their potential to target multiple microbes, has motivated the synthesis of AMPs and their relatives for developing antibiofilm agents for clinical purposes. Antibiofilm peptides (ABFPs) have been organized in databases that have allowed the building of prediction tools which have assisted in the discovery/design of new antibiofilm agents. However, the complex network approach has not yet been explored as an assistant tool for this aim. Herein, a kind of similarity network called the half-space proximal network (HSPN) is applied to represent/analyze the chemical space of ABFPs, aiming to identify privileged scaffolds for the development of next-generation antimicrobials that are able to target both planktonic and biofilm microbial forms. Such analyses also considered the metadata associated with the ABFPs, such as origin, other activities, targets, etc., in which the relationships were projected by multilayer networks called metadata networks (METNs). From the complex networks’ mining, a reduced but informative set of 66 ABFPs was extracted, representing the original antibiofilm space. This subset contained the most central to atypical ABFPs, some of them having the desired properties for developing next-generation antimicrobials. Therefore, this subset is advisable for assisting the search for/design of both new antibiofilms and antimicrobial agents. The provided ABFP motifs list, discovered within the HSPN communities, is also useful for the same purpose.

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Section: Resultsmentioning

confidence: 99%

Complex Networks Analyses of Antibiofilm Peptides: An Emerging Tool for Next-Generation Antimicrobials’ Discovery

et al. 2023

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“…The primary mechanism of action of AMPs is disrupting the cytoplasmic membrane of microorganisms and even cancer cells [ 79 , 80 , 81 , 82 ]. However, a handful of AMPs exert their effect intracellular by homing to organelles like the mitochondria and the nucleus and interacting with protein and nucleic acids [ 16 , 32 , 83 ].…”

Section: Discussionmentioning

confidence: 99%

Cell-Penetrating Antimicrobial Peptides with Anti-Infective Activity against Intracellular Pathogens

et al. 2022

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Cell-penetrating peptides (CPPs) are natural or engineered peptide sequences with the intrinsic ability to internalize into a diversity of cell types and simultaneously transport hydrophilic molecules and nanomaterials, of which the cellular uptake is often limited. In addition to this primordial activity of cell penetration without membrane disruption, multivalent antimicrobial activity accompanies some CPPs. Antimicrobial peptides (AMPs) with cell-penetrability exert their effect intracellularly, and they are of great interest. CPPs with antimicrobial activity (CPAPs) comprise a particular class of bioactive peptides that arise as promising agents against difficult-to-treat intracellular infections. This short review aims to present the antibacterial, antiparasitic, and antiviral effects of various cell-penetrating antimicrobial peptides currently documented. Examples include the antimicrobial effects of different CPAPs against bacteria that can propagate intracellularly, like Staphylococcus sp., Streptococcus sp., Chlamydia trachomatis, Escherichia coli, Mycobacterium sp., Listeria sp., Salmonella sp. among others. CPAPs with antiviral effects that interfere with the intracellular replication of HIV, hepatitis B, HPV, and herpes virus. Additionally, CPAPs with activity against protozoa of the genera Leishmania, Trypanosoma, and Plasmodium, the etiological agents of Leishmaniasis, Chagas’ Disease, and Malaria, respectively. The information provided in this review emphasizes the potential of multivalent CPAPs, with anti-infective properties for application against various intracellular infections. So far, CPAPs bear a promise of druggability for the translational medical use of CPPs alone or in combination with chemotherapeutics. Moreover, CPAPs could be an exciting alternative for pharmaceutical design and treating intracellular infectious diseases.

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“…Particularly powerful characteristics of CPPs are the ability to not only penetrate the cellular membrane but also home in on certain organelles to increase the precision of target site specificity. Targeting specific organelles within the cell when it comes to fighting cancer is important due to the fact that targeted delivery to the specific intracellular targets can result in enhanced therapeutic efficacy and reduced toxicity [ 84 , 85 , 86 , 87 , 88 ]. Combining a specific organelle-locator sequence to the CPP, along with the therapeutic cargo, results in even greater control over the delivery of anti-cancer drugs.…”

Section: Intracellular-targeted Delivery By Cppsmentioning

confidence: 99%

Cell-Penetrating Peptides (CPPs) as Therapeutic and Diagnostic Agents for Cancer

Bottens

Yamada

2022

Cancers

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Cell-Penetrating Peptides (CPPs) are short peptides consisting of <30 amino acids. Their ability to translocate through the cell membrane while carrying large cargo biomolecules has been the topic of pre-clinical and clinical trials. The ability to deliver cargo complexes through membranes yields potential for therapeutics and diagnostics for diseases such as cancer. Upon cellular entry, some CPPs have the ability to target specific organelles. CPP-based intracellular targeting strategies hold tremendous potential as they can improve efficacy and reduce toxicities and side effects. Further, recent clinical trials show a significant potential for future CPP-based cancer treatment. In this review, we summarize recent advances in CPPs based on systematic searches in PubMed, Embase, Web of Science, and Scopus databases until 30 September 2022. We highlight targeted delivery and explore the potential uses for CPPs as diagnostics, drug delivery, and intrinsic anti-cancer agents.

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Designed Multifunctional Peptides for Intracellular Targets

Cited by 11 publications

References 320 publications

Complex Networks Analyses of Antibiofilm Peptides: An Emerging Tool for Next-Generation Antimicrobials’ Discovery

Complex Networks Analyses of Antibiofilm Peptides: An Emerging Tool for Next-Generation Antimicrobials’ Discovery

Cell-Penetrating Antimicrobial Peptides with Anti-Infective Activity against Intracellular Pathogens

Cell-Penetrating Peptides (CPPs) as Therapeutic and Diagnostic Agents for Cancer

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