Inhibiting the VIM-2 Metallo-β-Lactamase by Graphene Oxide and Carbon Nanotubes

Huang, Po‐Jung Jimmy; Pautler, Rachel; Shanmugaraj, Jenitta; Labbé, Geneviève; Liu, Juewen

doi:10.1021/acsami.5b01954

Cited by 24 publications

(27 citation statements)

References 44 publications

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“…Moreover, protein adsorption by nanomaterials, not least by GO, which presents a vast surface for protein binding, can lead to inhibition of enzyme activity. Hence, recent studies have shown that carbon-based nanomaterials can inhibit the bacterial enzyme, VIM-2 belonging to the clinically relevant class of metallo-β-lactamases that provide resistance to a broad spectrum of antibiotics including penicillin; the inhibition was noncompetitive and was attributed to hydrophobic interactions with the enzyme [90]. Moreover, adsorption of VIM-2 was further probed using protein displacement assays and it could not displace or be displaced by BSA.…”

Section: Bio-corona Formation On Carbon-based Nanomaterialsmentioning

confidence: 99%

Biological interactions of carbon-based nanomaterials: From coronation to degradation

Bhattacharya

Mukherjee

Gallud

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

357

226

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Carbon-based nanomaterials including single- and multi-walled carbon nanotubes, graphene oxide, fullerenes and nanodiamonds are potential candidates for various applications in medicine such as drug delivery and imaging. However, the successful translation of nanomaterials for biomedical applications is predicated on a detailed understanding of the biological interactions of these materials. Indeed, the potential impact of the so-called bio-corona of proteins, lipids, and other biomolecules on the fate of nanomaterials in the body should not be ignored. Enzymatic degradation of carbon-based nanomaterials by immune-competent cells serves as a special case of bio-corona interactions with important implications for the medical use of such nanomaterials. In the present review, we highlight emerging biomedical applications of carbon-based nanomaterials. We discuss recent studies on nanomaterial ‘coronation’ and how this impacts on biodistribution and targeting along with studies on the enzymatic degradation of carbon-based nanomaterials, and the role of surface modification of nanomaterials for these biological interactions.

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Section: Bio-corona Formation On Carbon-based Nanomaterialsmentioning

confidence: 99%

Biological interactions of carbon-based nanomaterials: From coronation to degradation

Bhattacharya

Mukherjee

Gallud

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

357

226

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“… 38 Verona integron-encoded-2 (VIM-2), a subclass of MBLs, is a negatively charged protein with Zn 2+ -dependent enzyme activity. 39 In a systematic investigation by Huang and co-workers, 40 the effects of various nanomaterials on VIM-2 catalytic activity were explored. Among the ten nanomaterials examined with different surface properties, graphene oxide (GO) and carbon nanotube (CNT) exerted significant inhibitory effects on VIM-2 in a dose-dependent manner ( Figure 7A and B ).…”

Section: Nanozyme As β-Lactamase Inhibitorsmentioning

confidence: 99%

Nanozymes as Enzyme Inhibitors

Huang¹,

Jiang²,

Wang³

et al. 2021

IJN

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Nanozyme is a type of nanomaterial with intrinsic enzyme-like activity. Following the discovery of nanozymes in 2007, nanozyme technology has become an emerging field bridging nanotechnology and biology, attracting research from multi-disciplinary areas focused on the design and synthesis of catalytically active nanozymes. However, various types of enzymes can be mimicked by nanomaterials, and our current understanding of nanozymes as enzyme inhibitors is limited. Here, we provide a brief overview of the utility of nanozymes as inhibitors of enzymes, such as R-chymotrypsin (ChT), β-galactosidase (β-Gal), β-lactamase, and mitochondrial F0F1-ATPase, and the mechanisms underlying inhibitory activity. The advantages, challenges and future research directions of nanozymes as enzyme inhibitors for biomedical research are further discussed.

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“…Three azolylthioacetamide derivatives reported by Xiang et al were characterized as inhibitors with mixed inhibition mechanism (competitive and uncompetitive), however, their uncompetitive inhibition mechanism and binding site has not been reported [81]. At the time of writing, allosteric inhibition has proven a viable strategy only by using macromolecules, such as DNA nanoribbons, DNA aptamers, camelid nanobodies, graphene oxides and nanotubes [82][83][84][85].…”

Section: Allosteric Effectors and Mechanisms In Class B Blsmentioning

confidence: 99%

Can We Exploit β-Lactamases Intrinsic Dynamics for Designing More Effective Inhibitors?

et al. 2020

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β-lactamases (BLs) represent the most frequent cause of antimicrobial resistance in Gram-negative bacteria. Despite the continuous efforts in the development of BL inhibitors (BLIs), new BLs able to hydrolyze the last developed antibiotics rapidly emerge. Moreover, the insurgence rate of effective mutations is far higher than the release of BLIs able to counteract them. This results in a shortage of antibiotics that is menacing the effective treating of infectious diseases. The situation is made even worse by the co-expression in bacteria of BLs with different mechanisms and hydrolysis spectra, and by the lack of inhibitors able to hit them all. Differently from other targets, BL flexibility has not been deeply exploited for drug design, possibly because of the small protein size, for their apparent rigidity and their high fold conservation. In this mini-review, we discuss the evidence for BL binding site dynamics being crucial for catalytic efficiency, mutation effect, and for the design of new inhibitors. Then, we report on identified allosteric sites in BLs and on possible allosteric inhibitors, as a strategy to overcome the frequent occurrence of mutations in BLs and the difficulty of competing efficaciously with substrates. Nevertheless, allosteric inhibitors could work synergistically with traditional inhibitors, increasing the chances of restoring bacterial susceptibility towards available antibiotics.

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Inhibiting the VIM-2 Metallo-β-Lactamase by Graphene Oxide and Carbon Nanotubes

Cited by 24 publications

References 44 publications

Biological interactions of carbon-based nanomaterials: From coronation to degradation

Biological interactions of carbon-based nanomaterials: From coronation to degradation

Nanozymes as Enzyme Inhibitors

Can We Exploit β-Lactamases Intrinsic Dynamics for Designing More Effective Inhibitors?

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