Effect of N- and C-Terminal Modifications on Cytotoxic Properties of Antimicrobial Peptide Tachyplesin I

Kuzmin, Denis; Emelianova, Anna A.; Kalashnikova, M. B.; Panteleev, Pavel V.; Ovchinnikova, Tatiana V.

doi:10.1007/s10517-017-3705-2

Cited by 24 publications

(12 citation statements)

References 11 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: 73%

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: 73%

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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“…The peptide DRGN-2 was derived from VK-CATH4.1 by replacing the glycine residue at position 18 of the wild-type sequence with alanine in order to increase the helical propensity of the peptide [38]. In DRGN-3 the N-terminal amine of DRGN-2 is acetylated and its C-terminal carboxy group is amidated in order to reduce susceptibility to proteolytic degradation [39]. These modifications, however, had no significant effect on antimicrobial activity, showing little to no positive contribution from the glycine to alanine substitution nor from capping of the N- and C-termini.…”

Section: Resultsmentioning

confidence: 99%

Komodo-dragon cathelicidin-inspired peptides are antibacterial against carbapenem-resistant Klebsiella pneumoniae

Hitt

Bishop

Hoek

2020

Journal of Medical Microbiology

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Introduction. The rise of carbapenem-resistant enterobacteriaceae (CRE) is a growing crisis that requires development of novel therapeutics. Hypothesis. To this end, cationic antimicrobial peptides (CAMPs) represent a possible source of new potential therapeutics to treat difficult pathogens such as carbapenem-resistant Klebsiella pneumoniae (CRKP), which has gained resistance to many if not all currently approved antibiotics, making treatment difficult. Aim. To examine the anti-CRKP antimicrobial activity of the predicted cathelicidins derived from Varanus komodoensis (Komodo dragon) as well as synthetic antimicrobial peptides that we created. Methodology. We determined the minimum inhibitory concentrations of the peptides against CRKP. We also characterized the abilities of these peptides to disrupt the hyperpolarization of the bacterial membrane as well as their ability to form pores in the membrane. Results. We did not observe significant anti-CRKP activity for the predicted native Komodo cathelicidin peptides. We found that the novel peptides DRGN-6,-7 and -8 displayed significant antimicrobial activity against CRKP with MICs of 4–8 µg ml−1. DRGN-6 peptide was the most effective peptide against CRKP. Unfortunately, these peptides showed higher than desired levels of hemolysis, although in vivo testing in the waxworm Galleria mellonella showed no mortality associated with treatment by the peptide; however, CRKP-infected waxworms treated with peptide did not show an improvement in survival. Conclusion. Given the challenges of treating CRKP, identification of peptides with activity against it represents a promising avenue for further research. Given DRGN-6′s similar level of activity to colistin, DRGN-6 is a promising template for the development of novel antimicrobial peptide-based therapeutics.

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“… 290 Similarly, Ovchinnikova and co-workers showed that the proteolytic stability of tachyplesin I was enhanced compared to the unmodified AMP following N-acetylation and C-amidation. 291 …”

Section: Chemical Synthesis Of Ampsmentioning

confidence: 99%

The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions

et al. 2021

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Effect of N- and C-Terminal Modifications on Cytotoxic Properties of Antimicrobial Peptide Tachyplesin I

Cited by 24 publications

References 11 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

Komodo-dragon cathelicidin-inspired peptides are antibacterial against carbapenem-resistant Klebsiella pneumoniae

The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions

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