Targeting Intracellular Pathogenic Bacteria with Unnatural Proline‐Rich Peptides: Coupling Antibacterial Activity with Macrophage Penetration

“…1). P14LRR is a small de novo proline rich antimicrobial peptide that forms a cationic amphiphilic polyproline helix and demonstrates broad-spectrum efficacy against pathogenic bacteria [13,14]. P14LRR is non-hemolytic and highly stable to proteases.…”

Section: Introductionmentioning

confidence: 99%

Targeting biofilms and persisters of ESKAPE pathogens with P14KanS, a kanamycin peptide conjugate

Mohamed

Brezden

Mohammad

et al. 2017

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…Brezden et al recently reported interesting conjugates (Figure ), consisting of the aminoglycoside antibiotic kanamycin ( 85 ) with the CPP P14LRR ( 86 ), which when conjugated exhibited potent ATB activity against these intracellular pathogens . The CPP ( 86 ) previously demonstrated intrinsic ATB activity against intracellular Salmonella and Brucella bacteria . In Brezden et al's study, kanamycin ( 85 ) was linked to ( 86 ), with or without a cleavable disulfide linkage, to form the conjugates ( 87 ) and ( 88 ) (Figure ).…”

Section: Trojan Horse Approaches To Overcome Antimicrobial Resistancementioning

confidence: 99%

“…211 The CPP (86) previously demonstrated intrinsic ATB activity against intracellular Salmonella and Brucella bacteria. 212 In Brezden et al's study, kanamycin (85) was linked to (86), with or without a cleavable disulfide linkage, to form the conjugates (87) and (88) (Figure 16). This attachment increased the overall net positive charge of the conjugates (from +8 to +12), therefore, facilitating the penetration and accumulation of the drug into J774A.1 host cells.…”

mentioning

confidence: 99%

Drug delivery systems designed to overcome antimicrobial resistance

Pham

Loupias

Dassonville‐Klimpt

et al. 2019

Medicinal Research Reviews

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Antimicrobial resistance has emerged as a huge challenge to the effective treatment of infectious diseases. Aside from a modest number of novel anti‐infective agents, very few new classes of antibiotics have been successfully developed for therapeutic use. Despite the research efforts of numerous scientists, the fight against antimicrobial (ATB) resistance has been a longstanding continued effort, as pathogens rapidly adapt and evolve through various strategies, to escape the action of ATBs. Among other mechanisms of resistance to antibiotics, the sophisticated envelopes surrounding microbes especially form a major barrier for almost all anti‐infective agents. In addition, the mammalian cell membrane presents another obstacle to the ATBs that target intracellular pathogens. To negotiate these biological membranes, scientists have developed drug delivery systems to help drugs traverse the cell wall; these are called “Trojan horse” strategies. Within these delivery systems, ATB molecules can be conjugated with one of many different types of carriers. These carriers could include any of the following: siderophores, antimicrobial peptides, cell‐penetrating peptides, antibodies, or even nanoparticles. In recent years, the Trojan horse‐inspired delivery systems have been increasingly reported as efficient strategies to expand the arsenal of therapeutic solutions and/or reinforce the effectiveness of conventional ATBs against drug‐resistant microbes, while also minimizing the side effects of these drugs. In this paper, we aim to review and report on the recent progress made in these newly prevalent ATB delivery strategies, within the current context of increasing ATB resistance.

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“…BnPRP1 from Brassica napus ( Figure 3 c) like many other proline-rich AMPs (PrAMPs) forms random coils with little amount of α-helix composition that engage in a non-lytic modes of bacterial inactivation [ 69 ]. Since proline is incompatible with α-helical or β-sheet conformation, its frequent occurrence in a polypeptide sequence causes a conformational rearrangement that forces the molecule to adopt the polyproline II (PPII) helical structure [ 70 , 71 , 72 ] and ample evidence suggest that the PPII conformation may be the biologically active form for all PrAMP [ 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 ].…”

Section: Diverse Sources Of Ampsmentioning

confidence: 99%

Bioinspired Designs, Molecular Premise and Tools for Evaluating the Ecological Importance of Antimicrobial Peptides

2018

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This review article provides an overview of recent developments in antimicrobial peptides (AMPs), summarizing structural diversity, potential new applications, activity targets and microbial killing responses in general. The use of artificial and natural AMPs as templates for rational design of peptidomimetics are also discussed and some strategies are put forward to curtail cytotoxic effects against eukaryotic cells. Considering the heat-resistant nature, chemical and proteolytic stability of AMPs, we attempt to summarize their molecular targets, examine how these macromolecules may contribute to potential environmental risks vis-à-vis the activities of the peptides. We further point out the evolutional characteristics of the macromolecules and indicate how they can be useful in designing target-specific peptides. Methods are suggested that may help to assess toxic mechanisms of AMPs and possible solutions are discussed to promote the development and application of AMPs in medicine. Even if there is wide exposure to the environment like in the hospital settings, AMPs may instead contribute to prevent healthcare-associated infections so long as ecotoxicological aspects are considered.

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Targeting Intracellular Pathogenic Bacteria with Unnatural Proline‐Rich Peptides: Coupling Antibacterial Activity with Macrophage Penetration

Cited by 20 publications

References 34 publications

Targeting biofilms and persisters of ESKAPE pathogens with P14KanS, a kanamycin peptide conjugate

Targeting biofilms and persisters of ESKAPE pathogens with P14KanS, a kanamycin peptide conjugate

Drug delivery systems designed to overcome antimicrobial resistance

Bioinspired Designs, Molecular Premise and Tools for Evaluating the Ecological Importance of Antimicrobial Peptides

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