Gramicidin Peptide to Combat Antibiotic Resistance: A Review

Pavithrra, G.; Rajasekaran, R.

doi:10.1007/s10989-019-09828-0

Cited by 26 publications

(26 citation statements)

References 78 publications

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“…The L-Trp residue at position 11 in gramicidin A is replaced by L-Phe in gramicidin B and L-Tyr in gramicidin C, and each analogue is individually active against pathogenic bacteria. [218][219][220][221] When injected intravenously, gramicidin D exhibits toxicity in mice and therefore cannot be used to treat systemic infections. However, it is highly effective via topical application and was used during World War II to treat wounds and ulcers, becoming the first AMP to be commercially manufactured.…”

Section: (Non)ribosomally-synthesised Amps and The Current Clinical Landscapementioning

confidence: 99%

The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions

et al. 2021

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Section: (Non)ribosomally-synthesised Amps and The Current Clinical Landscapementioning

confidence: 99%

The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions

et al. 2021

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“…Gramicidin D and S are considered ionophores as they bind to the membrane of the bacteria to form pores, leading to extensive efflux of the ions and solutes and disrupting intracellular functions. Gramicidin D consists of gramicidin A, B, and C. Interestingly, gramicidin A also shows anticancer activity by inducing metabolic dysfunction and energy depletion, which leads to suppression of cell growth and angiogenesis in renal cell carcinoma [293,294].…”

Section: Amp With Antibacterial Effectsmentioning

confidence: 99%

Discovery, Optimization, and Clinical Application of Natural Antimicrobial Peptides

et al. 2021

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Antimicrobial peptides (AMPs) are widespread in multicellular organisms. These structurally diverse molecules are produced as the first line of defense against pathogens such as bacteria, viruses, fungi, and parasites. Also known as host defense peptides in higher eukaryotic organisms, AMPs display immunomodulatory and anticancer activities. During the last 30 years, technological advances have boosted the research on antimicrobial peptides, which have also attracted great interest as an alternative to tackling the antimicrobial resistance scenario mainly provoked by some bacterial and fungal pathogens. However, the introduction of natural AMPs in clinical trials faces challenges such as proteolytic digestion, short half-lives, and cytotoxicity upon systemic and oral application. Therefore, some strategies have been implemented to improve the properties of AMPs aiming to be used as effective therapeutic agents. In the present review, we summarize the discovery path of AMPs, focusing on preclinical development, recent advances in chemical optimization and peptide delivery systems, and their introduction into the market.

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“…Because available SAR data are limited, it remains unclear how the ion channel function of 1 relates to its antibacterial and cytotoxic activities. Extensive exploration and biological evaluation of the analogues of 1 are necessary for developing lead compounds for systemic antibiotics or anticancer agents 35 – 37 .…”

Section: Introductionmentioning

confidence: 99%

Discovery of gramicidin A analogues with altered activities by multidimensional screening of a one-bead-one-compound library

et al. 2020

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Gramicidin A (1) is a peptide antibiotic that disrupts the transmembrane ion concentration gradient by forming an ion channel in a lipid bilayer. Although long used clinically, it is limited to topical application because of its strong hemolytic activity and mammalian cytotoxicity, likely arising from the common ion transport mechanism. Here we report an integrated high-throughput strategy for discovering analogues of 1 with altered biological activity profiles. The 4096 analogue structures are designed to maintain the charge-neutral, hydrophobic, and channel forming properties of 1. Synthesis of the analogues, tandem mass spectrometry sequencing, and 3 microscale screenings enable us to identify 10 representative analogues. Re-synthesis and detailed functional evaluations find that all 10 analogues share a similar ion channel function, but have different cytotoxic, hemolytic, and antibacterial activities. Our large-scale structure-activity relationship studies reveal the feasibility of developing analogues of 1 that selectively induce toxicity toward target organisms.

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Gramicidin Peptide to Combat Antibiotic Resistance: A Review

Cited by 26 publications

References 78 publications

The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions

The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions

Discovery, Optimization, and Clinical Application of Natural Antimicrobial Peptides

Discovery of gramicidin A analogues with altered activities by multidimensional screening of a one-bead-one-compound library

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