Cytotoxic Potential of the Novel Horseshoe Crab Peptide Polyphemusin III

Marggraf, Mariana B; Panteleev, Pavel V.; Emelianova, Anna A.; Sorokin, Maxim; Bolosov, Ilia A.; Buzdin, Anton; Kuzmin, Denis; Ovchinnikova, Tatiana V.

doi:10.3390/md16120466

Cited by 28 publications

(17 citation statements)

References 51 publications

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“…The C-amidated peptides TI–TIII lysed 66%, 56% and 41% of RBCs at 64 µM respectively (Figure 2b and Table 2). A similar trend but lower hemolytic activity had been reported for TI, TII, and TIII lacking C-terminal amidation at higher peptide concentrations [47], which is known to impact peptide activity [48,49].…”

Section: Resultssupporting

confidence: 74%

Characterization of Tachyplesin Peptides and Their Cyclized Analogues to Improve Antimicrobial and Anticancer Properties

Vernen

Harvey

Dias

et al. 2019

IJMS

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Tachyplesin I, II and III are host defense peptides from horseshoe crab species with antimicrobial and anticancer activities. They have an amphipathic β-hairpin structure, are highly positively-charged and differ by only one or two amino acid residues. In this study, we compared the structure and activity of the three tachyplesin peptides alongside their backbone cyclized analogues. We assessed the peptide structures using nuclear magnetic resonance (NMR) spectroscopy, then compared the activity against bacteria (both in the planktonic and biofilm forms) and a panel of cancerous cells. The importance of peptide-lipid interactions was examined using surface plasmon resonance and fluorescence spectroscopy methodologies. Our studies showed that tachyplesin peptides and their cyclic analogues were most potent against Gram-negative bacteria and melanoma cell lines, and showed a preference for binding to negatively-charged lipid membranes. Backbone cyclization did not improve potency, but improved peptide stability in human serum and reduced toxicity toward human red blood cells. Peptide-lipid binding affinity, orientation within the membrane, and ability to disrupt lipid bilayers differed between the cyclized peptide and the parent counterpart. We show that tachyplesin peptides and cyclized analogues have similarly potent antimicrobial and anticancer properties, but that backbone cyclization improves their stability and therapeutic potential.

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Section: Resultssupporting

confidence: 74%

Characterization of Tachyplesin Peptides and Their Cyclized Analogues to Improve Antimicrobial and Anticancer Properties

Vernen

Harvey

Dias

et al. 2019

IJMS

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“…Tachyplesin I from horseshoe crabs shows an antitumor activity; however, the action mode of tachyplesin I in tumor cells remains unclear (Li et al, 2017). The new antimicrobial peptide polyphemusin III can induce cell death by destroying the plasma membrane (Marggraf et al, 2018). Purified recombinant Factor C may be applied to inhibit inflammation and septic shock (Li et al, 2007).…”

Section: Hot Research Orientationmentioning

confidence: 99%

Research Development on Horseshoe Crab: A 30-Year Bibliometric Analysis

Luo

Miao

et al. 2020

Front. Mar. Sci.

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This review provides the updated information and analysis of research development on horseshoe crabs over the past 30 years and raises some suggestions for future studies on horseshoe crabs. Horseshoe crab is a unique marine species and attracts many scholars in various research fields. However, to date, the development of horseshoe crab research has not been analyzed and reported from a bibliometric perspective. Bibliometric analysis is a unique tool for evaluating the development of a specific research area by analyzing relevant publications and researchers from all over the world. In this study, Web of Science, Google Scholar, and PubMed were used to collect relevant data on horseshoe crabs. VOSviewer software was used to visualize cooperation and major keywords in horseshoe crab research. From 1989 to 2019, scholars emphasized the physiological characteristics, medical value, and ecological conservation of horseshoe crabs. Some topics in this field have gradually developed because of some reasons explained in this review. Some important or recent studies have been discussed, and some potential research topics for future research have been suggested.

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“…Although hydrophobicity and cationicity of the peptides are essential for their activity, beyond a limit these parameters do not improve antimicrobial activity 13,[15][16][17][18][19][20][21][22] . Highly hydrophobic peptides target neutrally charged mammalian cell membrane leading to a reduction in the selectivity of target 18,[23][24][25][26] . One of the major limitations in developing AMP as a therapeutic is peptide-mediated hemolysis or cytotoxicity against host cells 27 .…”

Section: Introductionmentioning

confidence: 99%

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2020

IJPSR

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Antimicrobial peptides are considered as promising and potential next-generation antibiotics on account of their broad spectrum of antimicrobial activity and unique mode of microbial killing. For therapeutic application, it is essential to consider the hemolytic or cytotoxic property of AMPs along with antimicrobial function. In the current study, an avian beta-defensin 7 (AvBD7) gene was identified from Corvus splendens. The predicted amino acid sequence showed the presence of β defensin core motif and three disulphide bridges. We analysed the interaction of wild and mutant analogues of mature Corvus AvBD7 dimer with neutral 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) that mimics mammalian membranes using molecular dynamics simulation studies. Hydrophobic residues at the N-terminus of each monomer were found to provide stability in the dimeric form. In both monomer and dimer, Asp3 and Asp4 interact with Tyr40 and Ser41 thereby helping in maintaining a claw shape at the C-terminus. During simulation, we found that the C-terminus claw region of wild dimer remained intact than its mutant analogs, and also wild AvBD7 exhibited a greater propensity to bind POPC membrane than its mutant analogs. Based on the membrane-peptide distance and number of hydrogen bonds formed between peptide and membrane, we conclude that the alanine mutant might be least hemolytic as it showed reduced propensity to bind to POPC membrane.

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Cytotoxic Potential of the Novel Horseshoe Crab Peptide Polyphemusin III

Cited by 28 publications

References 51 publications

Characterization of Tachyplesin Peptides and Their Cyclized Analogues to Improve Antimicrobial and Anticancer Properties

Characterization of Tachyplesin Peptides and Their Cyclized Analogues to Improve Antimicrobial and Anticancer Properties

Research Development on Horseshoe Crab: A 30-Year Bibliometric Analysis

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