Drug and dye binding induced folding of the intrinsically disordered antimicrobial peptide CM15

Zsila, Ferenc; Bősze, Szilvia; Horváti, Kata; Szigyártó, Imola Csilla; Beke‐Somfai, Tamás

doi:10.1039/c7ra05290a

Cited by 19 publications

(33 citation statements)

References 40 publications

(47 reference statements)

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“…As previously reported, the drug suramin (Sur) has proved to be an effective folding inducer with the disordered membrane‐active peptide CM15. To aid understanding of the structural effects of suramin on the interaction between CM15 and membranes, CD spectra in the presence of the interacting partners were collected.…”

Section: Resultsmentioning

confidence: 99%

“…This is in agreement with reported observations . On the basis of the results presented here and in previous studies, suramin triggers the disorder‐to‐order conformational transition of CM15. The characteristic positive/negative couplet corresponding to π–π* transitions at 195 and 208 nm, as well as the negative band due to the n–π* transition at 222 nm (Figure A), suggest α‐helical folding of CM15 .…”

Section: Resultsmentioning

confidence: 99%

“…The electrostatic repulsion between the charged side chains renders the solution structures of the majority of cationic AMPs intrinsically disordered (ID) with no discernible secondary structure . Upon membrane binding, an unstructured AMP undergoes a conformational change and folds into a well‐ordered—mostly α‐helical—structure .…”

Section: Introductionmentioning

confidence: 99%

“…However, the in vivo action of these peptides is a complex issue, possibly including numerous types of interactions with small‐molecule agents. Indeed, previous studies in our group have suggested that small molecules of both endogenous and synthetic origin can dramatically affect the structures of AMPs, potentially altering their mechanistic function, including their antimicrobial efficiency . Similarly, it has also been observed that several disordered AMP and protein sequences adopt ordered secondary structures induced by the lipid mediator lysophosphatidic acid; this indicates that the presence and use of such interactions might be widespread in organisms, a phenomenon far from being understood.…”

Section: Introductionmentioning

confidence: 99%

“…To shed more light on this issue, this study has focused on CM15, a short, linear, natively unfolded, synthetic hybrid AMP combined from the silk moth cecropin A and the bee venom peptide melittin. CM15 displays a potent broad‐spectrum antimicrobial activity, retaining the bactericidal effect of cecropins but lacking the strong haemolytic property of melittin . With a total charge of +6, it has a much higher average charge per residue than its congeners.…”

Section: Introductionmentioning

confidence: 99%

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Manipulating Active Structure and Function of Cationic Antimicrobial Peptide CM15 with the Polysulfonated Drug Suramin: A Step Closer to in Vivo Complexity

et al. 2019

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Antimicrobial peptides (AMPs) kill bacteria by targeting their membranes through various mechanisms involving peptide assembly, often coupled with disorder‐to‐order structural transition. However, for several AMPs, similar conformational changes in cases in which small organic compounds of both endogenous and exogenous origin have induced folded peptide conformations have recently been reported. Thus, the function of AMPs and of natural host defence peptides can be significantly affected by the local complex molecular environment in vivo; nonetheless, this area is hardly explored. To address the relevance of such interactions with regard to structure and function, we have tested the effects of the therapeutic drug suramin on the membrane activity and antibacterial efficiency of CM15, a potent hybrid AMP. The results provided insight into a dynamic system in which peptide interaction with lipid bilayers is interfered with by the competitive binding of CM15 to suramin, resulting in an equilibrium dependent on peptide‐to‐drug ratio and vesicle surface charge. In vitro bacterial tests showed that when CM15⋅suramin complex formation dominates over membrane binding, antimicrobial activity is abolished. On the basis of this case study, it is proposed that small‐molecule secondary structure regulators can modify AMP function and that this should be considered and could potentially be exploited in future development of AMP‐based antimicrobial agents.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Manipulating Active Structure and Function of Cationic Antimicrobial Peptide CM15 with the Polysulfonated Drug Suramin: A Step Closer to in Vivo Complexity

et al. 2019

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The Un(f)told Story of General Anesthesia

Zsila

2018

ChemBioChem

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Inhalational anesthetics are routinely employed in clinical practice to accomplish general anesthesia. Concerns have recently emerged regarding the deleterious impact of these volatile agents on cognitive performance, immune functions, and tumor recurrence and metastasis. These agents have been shown to modify the gene-expression pattern as well as cell signaling in tumor cells, but the underlying molecular mechanisms remain a matter of conjecture. Regulatory/signaling proteins either of cytosolic or membrane origin abundantly contain intrinsically disordered sequences, the conformational pliability of which is pivotal in their biological functions. It is well known that chloroform (an anesthetic itself), trifluoroethanol, hexafluoroisopropanol, and related haloalcohols markedly affect the structure of disordered proteins and protein regions by inducing folding, misfolding, or even aggregation. Taking into consideration the physicochemical similarities and protein interaction modes of these volatile solvents and inhaled anesthetics, it is postulated that administration of these drugs can also modify the secondary structure of disordered protein segments. Accordingly, pharmacological effects of anesthetics may, at least in part, be mediated by conformational perturbations of intrinsic disorder-based regulatory protein networks of cells.

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Peptide and protein in therapeutics

Shinde,

Atpadkar,

Swain

et al. 2024

Peptide and Protein Drug Delivery Using Polysaccharides

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Drug and dye binding induced folding of the intrinsically disordered antimicrobial peptide CM15

Abstract: Drug binding induces the disorder-to-order conformational transition of the natively unfolded antimicrobial peptide CM15.

Cited by 19 publications

References 40 publications

Manipulating Active Structure and Function of Cationic Antimicrobial Peptide CM15 with the Polysulfonated Drug Suramin: A Step Closer to in Vivo Complexity

Manipulating Active Structure and Function of Cationic Antimicrobial Peptide CM15 with the Polysulfonated Drug Suramin: A Step Closer to in Vivo Complexity

The Un(f)told Story of General Anesthesia

Peptide and protein in therapeutics

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