Lysine Analogue of Polymyxin B as a Significant Opportunity for Photodynamic Antimicrobial Chemotherapy

Guern, Florent Le; Ouk, Tan‐Sothéa; Ouk, Catherine; Vanderesse, Régis; Champavier, Yves; Pinault, Émilie; Sol, Vincent

doi:10.1021/acsmedchemlett.7b00360

Cited by 30 publications

(38 citation statements)

References 21 publications

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“…441–443 Porphyrins are macrocyclic tetrapyrrole photosensitizers found in biological catalytic and light-harvesting systems 444,445 that have been exploited in these types of multicomponent systems due to their inherent photophysical properties. 446,447 While the self-assembly of molecules consisting of a porphyrin conjugated to a peptidic component has been studied for various applications, 433,440,443,448,449 this section will focus on a the coassembly of low molecular weight peptides and porphyrins into hybrid supramolecular structures.…”

Section: Coassembly Of Low Molecular Weight Peptidesmentioning

confidence: 99%

Multicomponent peptide assemblies

2018

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Self-assembled peptide nanostructures have been increasingly exploited as functional materials for applications in biomedicine and energy. The emergent properties of these nanomaterials determine the applications for which they can be exploited. It has recently been appreciated that nanomaterials composed of multicomponent coassembled peptides often display unique emergent properties that have the potential to dramatically expand the functional utility of peptide-based materials. This review presents recent efforts in the development of multicomponent peptide assemblies. The discussion includes multicomponent assemblies derived from short low molecular weight peptides, peptide amphiphiles, coiled coil peptides, collagen, and β-sheet peptides. The design, structure, emergent properties, and applications for these multicomponent assemblies are presented in order to illustrate the potential of these formulations as sophisticated next-generation bio-inspired materials.

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Section: Coassembly Of Low Molecular Weight Peptidesmentioning

confidence: 99%

Multicomponent peptide assemblies

2018

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“…The concept of improving the uptake of a PS in bacterial cells due to the action of the AMP, or more broadly cationic peptide, has been studied and described. Within the last few years, the results on the activity of porphyrin or xanthenes combined with cationic peptides against the model Gram-positive ( S. aureus ) and Gram-negative (mostly Escherichia coli , P. aeruginosa ) species have been described ( Bourre et al, 2010 ; Yang et al, 2011 ; Liu et al, 2012 ; Dosselli et al, 2013 , 2014 ; Johnson et al, 2013 ; Costley et al, 2017 ; Le Guern et al, 2017 , 2018 ). In all the referenced work, however, the authors presented the construction of conjugates composed of a PS and AMP rather than mixing separate components.…”

Section: Discussionmentioning

confidence: 99%

Rose Bengal-Mediated Photoinactivation of Multidrug Resistant Pseudomonas aeruginosa Is Enhanced in the Presence of Antimicrobial Peptides

et al. 2018

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Due to the overuse of antibiotics in medicine and food production, and their targeted mechanism of action, an increasing rate in spreading of antibiotic resistance genes has been noticed. This results in inefficient therapy outcomes and higher mortality all over the world. Pseudomonas aeruginosa (carbapenem-resistant) is considered one of the top three critical species according to the World Health Organization’s priority pathogens list. This means that new drugs and/or treatments are needed to tackle infections caused by this bacterium. In this context search for new/alternative approaches that would overcome resistance to classical antimicrobials is of prime importance. The use of antimicrobial photodynamic inactivation (aPDI) and antimicrobial peptides (AMPs) is an efficient strategy to treat localized infections caused by multidrug-resistant P. aeruginosa. In this study, we have treated P. aeruginosa cells photodynamically in the presence and in the absence of AMP (CAMEL or pexiganan). The conditions for aPDI were as follows: rose bengal (RB) as a photosensitizing agent at 1–10 μM concentration, and subsequent irradiation with 514 nm-LED at 23 mW/cm2 irradiance. The analysis of cell number after the treatment has shown that the combined action of RB-mediated aPDI and cationic AMPs reduced the number of viable cells below the limit of detection (<1log10 CFU/ml). This was in contrast to no reduction or partial reduction after aPDI or AMP applied separately. Students t-test was applied to test the statistical significance of the results. Noteworthy, our treatment proved to be effective against all 35 clinical isolates of P. aeruginosa tested within this study, including those characterized as multiresistant. Moreover, we demonstrated that such treatment is safe and does not violate the growth dynamics of human keratinocytes (77.3–97.64% survival depending on the concentration of the studied compounds or their mixtures).

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“…The thiol-maleimide reaction is a widely used method to conjugate peptides and drugs, where a peptide sulfhydryl group reacts with a pre-installed maleimide group on the drug (Scheme 4) [201,203,204,241,242,243]. The reaction is selective and efficient across a variety of solvents across a wide pH range, and the thioether bond offers reasonable chemical stability.…”

Section: Linker and Conjugation Chemistrymentioning

confidence: 99%

“…Conjugation of Polymyxin B and antimicrobial porphyrin via a thiol-maleimide bond. Thiol-maleimide bond was formed between maleimide containing porphyrin and unprotected peptide polymyxin B with a cysteine residue [241]. …”

Section: Figures Schemes and Tablementioning

confidence: 99%

Peptide Conjugates with Small Molecules Designed to Enhance Efficacy and Safety

Finan

Mayer

et al. 2019

Molecules

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Peptides constitute molecular diversity with unique molecular mechanisms of action that are proven indispensable in the management of many human diseases, but of only a mere fraction relative to more traditional small molecule-based medicines. The integration of these two therapeutic modalities offers the potential to enhance and broaden pharmacology while minimizing dose-dependent toxicology. This review summarizes numerous advances in drug design, synthesis and development that provide direction for next-generation research endeavors in this field. Medicinal studies in this area have largely focused upon the application of peptides to selectively enhance small molecule cytotoxicity to more effectively treat multiple oncologic diseases. To a lesser and steadily emerging extent peptides are being therapeutically employed to complement and diversify the pharmacology of small molecule drugs in diseases other than just cancer. No matter the disease, the purpose of the molecular integration remains constant and it is to achieve superior therapeutic outcomes with diminished adverse effects. We review linker technology and conjugation chemistries that have enabled integrated and targeted pharmacology with controlled release. Finally, we offer our perspective on opportunities and obstacles in the field.

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Lysine Analogue of Polymyxin B as a Significant Opportunity for Photodynamic Antimicrobial Chemotherapy

Cited by 30 publications

References 21 publications

Multicomponent peptide assemblies

Multicomponent peptide assemblies

Rose Bengal-Mediated Photoinactivation of Multidrug Resistant Pseudomonas aeruginosa Is Enhanced in the Presence of Antimicrobial Peptides

Peptide Conjugates with Small Molecules Designed to Enhance Efficacy and Safety

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