Antimalarial Peptides: The Long and the Short of It

Bell, Angus

doi:10.2174/138161211797416057

Cited by 61 publications

(49 citation statements)

References 87 publications

(142 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Some AMPs of different origin are known to affect Plasmodium development in different phases of the biological cycle, from asexual blood stages (cecropin, melittin, magainin, dermaseptin S4) to sexual stages in the mosquito, where AMPs can block ookinetes viability (VIDA 1-3, scorpine) or oocyst formation (VIDA 1-3) (Bell 2011). A recent work by Carter and colleagues investigated the effect of 33 AMPs on Plasmodium early sporogonic stages, verifying that they did not alter mosquitoes' fitness (Carter et al 2013).…”

Section: Antimicrobial Peptides In Malariamentioning

confidence: 99%

See 1 more Smart Citation

Beyond Lysozyme: Antimicrobial Peptides Against Malaria

D’Alessandro

Tullio

Giribaldi

2014

Human and Mosquito Lysozymes

View full text Add to dashboard Cite

Antimicrobial peptides (AMPs) are short amino acidic sequences with less than 100 residues. They are the components of the innate immune system not only in humans but also in plants, insects, and primitive multicellular organisms. Their role is to counteract the microorganisms, which could be potentially pathogenic for the host. AMPs active against viruses, bacteria, fungi, and parasites have been described. Among the antiparasitic AMPs reported so far, some peptides affect Plasmodium development in different phases of the biological cycle, from asexual blood stages to sexual stages in the mosquito, where AMPs can block ookinetes viability or oocyst formation. AMPs with antimalarial activity derive from different organisms, especially insects, as well as amphibians. In malaria research, AMPs have been mainly proposed for the engineering of mosquitoes or parasites to reduce or interrupt the malaria parasite transmission. In this chapter, the different classes of antimalarial AMPs (defensins, cecropins, dermaseptins) or single peptides (scorpine, melittin, gambicin) are described. 91

show abstract

Section: Antimicrobial Peptides In Malariamentioning

confidence: 99%

“…A possible classification of antimalarial AMPs is described by Bell (2011). Cationic, amphipathic "host-defense" peptides such as defensins and cecropins were treated in this chapter.…”

Section: Other Antimalarial Ampsmentioning

confidence: 99%

Beyond Lysozyme: Antimicrobial Peptides Against Malaria

D’Alessandro

Tullio

Giribaldi

2014

Human and Mosquito Lysozymes

View full text Add to dashboard Cite

show abstract

“…The innate immune system produces an array of small peptides like defensins which in general target membranes [112]. Translating these small peptides into drugs meets obstacles of target site delivery through the gastrointestinal tract and delivery to the target site [113].…”

Section: Innate Host Defense Targets Membranesmentioning

confidence: 99%

“…This raises the question of innate system defense in these potential mammalian hosts. The trophozoite and schizont stages both have a greater permeability to low molecular weight solutes and are subject to osmotic lysis and this possibly makes the infected erythrocytes more susceptible to membrane targeting [112]. …”

Section: Innate Host Defense Targets Membranesmentioning

confidence: 99%

Plasmodium Drug Targets Outside the Genetic Control of the Parasite

Sullivan¹

2013

Current Pharmaceutical Design

View full text Add to dashboard Cite

Drug development often seeks to find “magic bullets” which target microbiologic proteins while not affecting host proteins. Paul Ehrlich tested methylene blue as an antimalarial but this dye was not superior to quinine. Many successful antimalarial therapies are “magic shotguns” which target many Plasmodium pathways with little interference in host metabolism. Two malaria drug classes, the 8-aminoquinolines and the artemisinins interact with cytochrome P450s and host iron protoporphyrin IX or iron, respectively, to generate toxic metabolites and/or radicals, which kill the parasite by interference with many proteins. The non 8-amino antimalarial quinolines like quinine or piperaquine bind heme to inhibit the process of heme crystallization, which results in multiple enzyme inhibition and membrane dysfunction. The quinolines and artemisinins are rapidly parasiticidal in contrast to metal chelators, which have a slower parasite clearance rate with higher drug concentrations. Iron chelators interfere with the artemisinins but otherwise represent a strategy of targeting multiple enzymes containing iron. Interest has been revived in antineoplastic drugs that target DNA metabolism as antimalarials. Specific drug targeting or investigation of the innate immunity directed to the more permeable trophozoite or schizont infected erythrocyte membrane has been under explored. Novel drug classes in the antimalarial development pipeline which either target multiple proteins or unchangeable cellular targets will slow the pace of drug resistance acquisition.

show abstract

“…Peptides and DNA intercalating agents have been widely tested for their antimalarial activity (14)(15)(16)(17). Some cell-penetrating peptides (CPPs), e.g., TP10 (18), and a number of DNA intercalators have been shown to have antimalarial activity (16,17).…”

mentioning

confidence: 99%

Assessment of SYBR Green I Dye-Based Fluorescence Assay for Screening Antimalarial Activity of Cationic Peptides and DNA Intercalating Agents

Bhatia

Gautam

et al. 2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

bThe SYBR green I (SG) dye-based fluorescence assay for screening antimalarial compounds is based on direct quantitation of parasite DNA. We show that DNA-interacting cationic cell-penetrating peptides (CPPs) and intercalating agents compete with SG dye to bind to DNA. Therefore, readouts of this assay, unlike those of the [ 3 H]hypoxanthine incorporation assay, for the antimalarial activity of the above DNA binding agents may be erroneous. In the case of CPPs, false readouts can be improved by the removal of excess peptides. Malaria continues to be a major public health problem in the 21st century. More than 200 million cases of malaria were reported in 2012, and the emergence of new drug-resistant strains of Plasmodium makes the situation more critical and alarming (1, 2). Chemoresistance, drug monotherapies, the easy availability of substandard drugs, and genetic polymorphism are some of the major causes of parasite drug resistance (3, 4). Thus, it is imperative to identify new antimalarial agents. For antimalarial drug screening, the [ 3 H]hypoxanthine incorporation assay has been a gold standard (5), while parasite lactate dehydrogenase (pLDH)-(6) and histidine-rich protein II-based (7) assays are other widely used methods. However, these assays are expensive and involve multistep procedures and thus are difficult to utilize for highthroughput screening (8, 9). The SYBR green I (SG) dye-based fluorescence assay is a recently developed high-throughput screening method which has been reported to be as sensitive as the [ 3 H]hypoxanthine incorporation assay (8, 10). It has been extensively validated and compared with other known methods and is commonly used for high-throughput antimalarial drug screening (9,(11)(12)(13).Peptides and DNA intercalating agents have been widely tested for their antimalarial activity (14-17). Some cell-penetrating peptides (CPPs), e.g., TP10 (18), and a number of DNA intercalators have been shown to have antimalarial activity (16,17). Interestingly, it has been demonstrated that CPPs, like Tat, penetratin, and TP10, are efficient agents for the delivery of bioactive molecules across the plasma membrane barrier (19). It has also been shown that CPPs move to the nucleus and bind to the target DNA, forming peptide-DNA complexes (20, 21). Since SG dye, CPPs, and intercalating agents bind to DNA, the aim of the present study was to evaluate the suitability of an SG dye-based fluorescence assay for determining the antiplasmodial activity of DNA binding agents. CPPs, Tat, penetratin, TP10, P3, P8 (19,22), and control peptides (Table 1) were chemically synthesized (USV, Mumbai, India) with more than 95% purity. TP10 is a broad-spectrum antiparasitic CPP (18), while Tat has been shown to be nontoxic (at 50 M) to Plasmodium parasites (23). Synchronized Plasmodium falciparum 3D7 cultures at 2% parasitemia and 2% hematocrit were lysed (10) and treated with various concentrations (6.25 M to 100 M) of Tat, penetratin, TP10, and control peptides (control cyclic peptide [CP1] and control linear pe...

show abstract

Antimalarial Peptides: The Long and the Short of It

Cited by 61 publications

References 87 publications

Beyond Lysozyme: Antimicrobial Peptides Against Malaria

Beyond Lysozyme: Antimicrobial Peptides Against Malaria

Plasmodium Drug Targets Outside the Genetic Control of the Parasite

Assessment of SYBR Green I Dye-Based Fluorescence Assay for Screening Antimalarial Activity of Cationic Peptides and DNA Intercalating Agents

Contact Info

Product

Resources

About