A comparison of activity, toxicity, and conformation of tritrpticin and two TOAC-labeled analogues. Effects on the mechanism of action

Bozelli, José Carlos; Salay, Luiz Carlos; Arcísio-Miranda, Manoel; Procópio, Joaquim; Riciluca, Katie Cristina Takeuti; Silva, Pedro I.; Nakaie, Clóvis R.; Schreier, Shirley

doi:10.1016/j.bbamem.2019.183110

Cited by 8 publications

(6 citation statements)

References 74 publications

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“… 19 TRP3 was labeled with TOAC at its N-terminal extremity (TOAC 0 -TRP3), and internally, by substituting the proline residue in position five (TOAC5-TRP3) to elucidate its mechanism of action ( Figure 1A ), activity, toxicity, and conformational properties. 20 Both TOAC-labeled peptides presented similar activity against Escherichia coli (minimum inhibitory concentration [MIC] = 4.0, 1.3 and 1.9 μmol L −1 for TOAC 0 -TRP3, TOAC5-TRP3, and TRP3, respectively), and Micrococcus luteus (MIC ~4.0 and 1.1 μmol L −1 for TOAC-labeled peptides and TRP3, respectively) compared to non-labeled TRP3. 20 All of the peptides showed low hemolytic activity (<5%) at concentrations 25-fold higher than their MIC.…”

Section: Introductionmentioning

confidence: 99%

“… 20 Both TOAC-labeled peptides presented similar activity against Escherichia coli (minimum inhibitory concentration [MIC] = 4.0, 1.3 and 1.9 μmol L −1 for TOAC 0 -TRP3, TOAC5-TRP3, and TRP3, respectively), and Micrococcus luteus (MIC ~4.0 and 1.1 μmol L −1 for TOAC-labeled peptides and TRP3, respectively) compared to non-labeled TRP3. 20 All of the peptides showed low hemolytic activity (<5%) at concentrations 25-fold higher than their MIC. In addition, compared to its template TRP3, the labeled N-terminal extremity led to a similar complex structure, but was more effective at membrane permeabilization.…”

Section: Introductionmentioning

confidence: 99%

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Light-Emitting Probes for Labeling Peptides

Boaro

Ageitos

Torres

et al. 2020

Cell Reports Physical Science

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SUMMARY Peptides are versatile biopolymers composed of 2–100 amino acid residues that present a wide range of biological functions and constitute potential therapies for numerous diseases, partly due to their ability to penetrate cell membranes. However, their mechanisms of action have not been fully elucidated due to the lack of appropriate tools. Existing light-emitting probes are limited by their cytotoxicity and large size, which can alter peptide structure and function. Here, we describe the available fluorescent, bioluminescent, and chemiluminescent probes for labeling peptides, with a focus on minimalistic options.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Light-Emitting Probes for Labeling Peptides

Boaro

Ageitos

Torres

et al. 2020

Cell Reports Physical Science

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“…Interestingly, SPPS offers a precise modification of AMP primary sequences, to modulate their biological activity against different types of pathogens and evaluate structure–activity relationships. Moreover, the design of AMPs via chemical synthesis can incorporate unusual and nonnatural amino acids to study the backbone conformation, dynamics in the membrane, and solution and orientation of peptides [ 16 , 17 ], via spectroscopy techniques [ 18 , 19 ].…”

Section: Why Are Amps Highlighted In the Development Of New Antibiotics?mentioning

confidence: 99%

Challenge in the Discovery of New Drugs: Antimicrobial Peptides against WHO-List of Critical and High-Priority Bacteria

et al. 2021

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Bacterial resistance has intensified in recent years due to the uncontrolled use of conventional drugs, and new bacterial strains with multiple resistance have been reported. This problem may be solved by using antimicrobial peptides (AMPs), which fulfill their bactericidal activity without developing much bacterial resistance. The rapid interaction between AMPs and the bacterial cell membrane means that the bacteria cannot easily develop resistance mechanisms. In addition, various drugs for clinical use have lost their effect as a conventional treatment; however, the synergistic effect of AMPs with these drugs would help to reactivate and enhance antimicrobial activity. Their efficiency against multi-resistant and extensively resistant bacteria has positioned them as promising molecules to replace or improve conventional drugs. In this review, we examined the importance of antimicrobial peptides and their successful activity against critical and high-priority bacteria published in the WHO list.

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“…Labelling with the paramagnetic amino acid TOAC ( Figure 24 ) is a new strategy in the studies of conformation, dynamics, orientation, and physicochemical properties of AMPs [ 217 ]. Unexpectedly, labelling with TOAC increases activity against Gram-positive bacteria, as it was shown for Tritrpticin (TRP3; Figure 24 ), an AMP against bacteria and fungi [ 218 , 219 , 220 , 221 , 222 , 223 ].…”

Section: Unnatural Amino Acidsmentioning

confidence: 99%

“…Labelling TRP3 with TOAC (TOAC-VRRFPWWWPFLRR (T1) and VRRF-TOAC-WWWPFLRR (T2)) led to the increase in antibacterial activity against M. luteus (MIC T1 (μM) < 0.38; MIC T2 (μM) < 0.39) and E.coli (MIC T1 (μM) = 4; MIC T2 (μM) = 1.3), respect to TRP3 (MIC M.luteus (μM) = 1.1; MIC E.coli (μM) = 1.9) TOAC presented a greater freedom of motion at the N-terminus rather than at the internal position. Analogously to TRP3, both TOAC-labelled peptides, showed prominent cation selectivity [ 217 ].…”

Section: Unnatural Amino Acidsmentioning

confidence: 99%

The Best Peptidomimetic Strategies to Undercover Antibacterial Peptides

Lachowicz

Szczepski

Scano

et al. 2020

IJMS

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Health-care systems that develop rapidly and efficiently may increase the lifespan of humans. Nevertheless, the older population is more fragile, and is at an increased risk of disease development. A concurrently growing number of surgeries and transplantations have caused antibiotics to be used much more frequently, and for much longer periods of time, which in turn increases microbial resistance. In 1945, Fleming warned against the abuse of antibiotics in his Nobel lecture: “The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant”. After 70 years, we are witnessing the fulfilment of Fleming’s prophecy, as more than 700,000 people die each year due to drug-resistant diseases. Naturally occurring antimicrobial peptides protect all living matter against bacteria, and now different peptidomimetic strategies to engineer innovative antibiotics are being developed to defend humans against bacterial infections.

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A comparison of activity, toxicity, and conformation of tritrpticin and two TOAC-labeled analogues. Effects on the mechanism of action

Cited by 8 publications

References 74 publications

Light-Emitting Probes for Labeling Peptides

Light-Emitting Probes for Labeling Peptides

Challenge in the Discovery of New Drugs: Antimicrobial Peptides against WHO-List of Critical and High-Priority Bacteria

The Best Peptidomimetic Strategies to Undercover Antibacterial Peptides

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