Modular sub-monomeric cell-penetrating guanidine-rich peptoids – synthesis, assembly and biological evaluation

Marouseau, Étienne; Neckebroeck, Albane; Larkin, Heidi; Roux, Antoine Le; Volkov, Léonid; Lavoie, Christine; Marsault, Éric

doi:10.1039/c6ra27898a

Cited by 10 publications

(25 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a result, antimicrobials are unable to reach intracellular targets or intracellular microbes. This in turn restricts the arsenal of drugs that can be employed to efficiently target intracellular microbes [30]. Existing studies have shown the use of viral vectors as shuttle for AMPs or membrane disruption for delivery, but this can potentially result in unintended cytotoxicity.…”

Section: Cell Penetrating Peptoidsmentioning

confidence: 99%

Novel tetrameric cell penetrating antimicrobial peptoids effective against mycobacteria and drug-resistant Staphylococcus aureus

Fleck¹,

Mukherjee²,

Tram³

et al. 2022

Front. Biosci. (Landmark Ed)

View full text Add to dashboard Cite

Background: Antimicrobial peptides (AMPs) are short, cationic, amphipathic molecules that have gained tremendous popularity as alternatives to traditional antibiotics due to their lower propensity to develop bacterial resistance. However, the clinical developability of AMPs remains impeded due to shortcomings such as proteolytic instability and poor penetration leading to low bioavailability. Aims: To improve the access of AMPs to cells and subsequent bacteria killing, we evaluated the cell-penetrating and antimicrobial properties of three novel libraries of synthetic peptoids using Minimum Inhibitory Concentration, killing efficacy and membrane permeabilization assays against mycobacteria and Staphylococcus aureus. In addition, we investigated cell selectivity using mammalian cells to assess peptoid toxicity. Results: We showed that short tetrameric Rhodamine B-labeled peptoids composed of a balance of aromatic and lipophilic residues have potent selective antimicrobial activity against a range of microorganisms. The most potent candidates were active against drug-resistant S. aureus isolates as well as mycobacterial strains, with cell penetrating capabilities reported in HeLa and RAW 264.7 macrophage cells. Conclusions: These data suggest that peptoids with novel dual functionalities may potentially be an interesting class of therapeutics and/or molecular delivery agents for anti-infective purposes.

show abstract

Section: Cell Penetrating Peptoidsmentioning

confidence: 99%

Novel tetrameric cell penetrating antimicrobial peptoids effective against mycobacteria and drug-resistant Staphylococcus aureus

Fleck¹,

Mukherjee²,

Tram³

et al. 2022

Front. Biosci. (Landmark Ed)

View full text Add to dashboard Cite

show abstract

“…[84] CPPos with branched cationic side chains, such as guanidine moieties, have been reported, and a CPPos with eight guanidino moieties exhibited efficient cellular uptake. [85] Peptoid modification, such as via acetoxymethyl (AM) esterification, can be used to aid the delivery of some cargos. AM-esterified peptoids that had been conjugated to 4,5,6,7-tetrabromo-1H-benzimidazole (TBBz) efficiently penetrated cell membranes and inhibited casein kinase 2 within cells.…”

Section: P E R S O N a L A C C O U N T T H E C H E M I C A L R E C O R Dmentioning

confidence: 99%

De Novo Design of Cell‐Penetrating Foldamers

Yokoo

Misawa

Demizu

2020

The Chemical Record

View full text Add to dashboard Cite

Cell‐penetrating peptides (CPPs) have gained much attention as carriers of hydrophilic molecules, such as drugs, peptides, and nucleic acids, into cells. CPPs are mainly composed of cationic amino acid residues, which play an important role in their intracellular uptake via interactions with acidic groups on cell surfaces. In addition, the secondary structures of CPPs also affect their cell‐membrane permeability. Based on this knowledge, a variety of cell‐penetrating foldamers (oligomers that form organized secondary structures) have been developed to date. In this account, we describe recent attempts to develop cell‐penetrating foldamers containing various building blocks, and their application as DDS carriers.

show abstract

“…In this work, they delivered the coenzyme Q10 (CoQ10) derivative named Pepto Q into plant mitochondria by using a polyguanidine peptoid as a delivery apparatus (compound 23 ) . Like its peptide counterpart, polyguanidine peptoid also enables the cellular transport of conjugated molecules. − It was proposed that Pepto Q was internalized via clathrin-dependent endocytosis, accumulated first in endosomes and then in the ER, and then transported to the intermembrane space of the mitochondria in two steps.…”

Section: Peptidomimetic-based Mitochondrial Delivery Strategymentioning

confidence: 99%

Mitochondrion-Targeting Peptides and Peptidomimetics: Recent Progress and Design Principles

et al. 2019

View full text Add to dashboard Cite

Mitochondria are multifunctional subcellular organelles whose operations encompass energy production, signal transduction, and metabolic regulation. Given their wide range of roles, they have been studied extensively as a potential therapeutic target for the treatment of various diseases, including cancer, diabetes, and neurodegenerative diseases. Mitochondrion-mediated pathways have been identified as promising targets in the context of these diseases. However, the delivery of specific probes and drugs to the mitochondria is one of the major problems that remains to be solved. Over the past decade, much effort has been devoted to developing mitochondrion-targeted delivery methods based on the membrane characteristics and the protein import machinery of mitochondria. While various methods utilizing small molecules to polymeric particles have been introduced, it is notable that many of these compounds share common structural elements and physicochemical properties for optimal selectivity and efficiency. In this Perspective, we will review the most recently developed mitochondrion-targeting peptides and peptidomimetics to outline the key aspects of structural requirements and design principles. We will also discuss successful and potential applications of mitochondrial delivery to assess opportunities and challenges in the targeting of mitochondria.

show abstract

Modular sub-monomeric cell-penetrating guanidine-rich peptoids – synthesis, assembly and biological evaluation

Abstract: Development of a guanidinium-rich transporters toolset to study GAG-mediated cell permeation.

Cited by 10 publications

References 45 publications

Novel tetrameric cell penetrating antimicrobial peptoids effective against mycobacteria and drug-resistant Staphylococcus aureus

Novel tetrameric cell penetrating antimicrobial peptoids effective against mycobacteria and drug-resistant Staphylococcus aureus

De Novo Design of Cell‐Penetrating Foldamers

Mitochondrion-Targeting Peptides and Peptidomimetics: Recent Progress and Design Principles

Contact Info

Product

Resources

About