Metallo-β-Lactamases and Aptamer-Based Inhibition

Schlesinger, Sara Rae; Lahousse, Mieke; Foster, Taylor O.; Kim, Sung-Kun

doi:10.3390/ph4020419

Cited by 21 publications

(21 citation statements)

References 28 publications

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“…Оба фермента не ингибировались аптамером, что показывает его высокую специфичность к целевому энзиму. Тесты на B. cereus аптамера с β-лактамным антибиотиком (цефалексин) показали супрессию роста культуры в течение 20 ч при 30°С [28].…”

Section: аптамеры ингибирующие бактериальные ферментыunclassified

Aptamers in the Treatment of Bacterial Infections: Problems and Prospects

et al. 2016

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Aptamers are short single-stranded oligonucleotides which are selected via targeted chemical evolution in vitro to bind a molecular target of interest. The aptamer selection technology is designated as SELEX (Systematic evolution of ligands by exponential enrichment). SELEX enables isolation of oligonucleotide aptamers binding a wide range of targets of interest with little respect for their nature and molecular weight. A number of applications of aptamer selection were developed ranging from biosensor technologies to antitumor drug discovery. First aptamer-based pharmaceutical (Macugen) was approved by FDA for clinical use in 2004, and since then more than ten aptamer-based drugs undergo various phases of clinical trials. From the medicinal chemist’s point of view, aptamers represent a new class of molecules suitable for the development of new therapeutics. Due to the stability, relative synthesis simplicity, and development of advanced strategies of target specific molecular selection, aptamers attract increased attention of drug discovery community. Difficulties of the development of next-generation antibiotics basing on the conventional basis of combinatorial chemistry and high-throughput screening have also amplified the interest to aptamer-based therapeutic candidates. The present article reviews the investigations focused on the development of antibacterial aptamers and discusses the potential and current limitations of the use of this type of therapeutic molecules.

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Section: аптамеры ингибирующие бактериальные ферментыunclassified

Aptamers in the Treatment of Bacterial Infections: Problems and Prospects

et al. 2016

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“…For example, β -lactamases are responsible for most of the antibiotic-resistant activity in bacterial cells. Kim and coworkers have selected DNA aptamers against metallo-β -lactamases, for which no clinically useful inhibitors are available (Kim et al 2009, Schlesinger et al 2011. Quite surprisingly, the functional aptamer was determined to be just a 10-mer DNA hairpin with three base pairs in the stem region and a 4-nucleotide loop.…”

Section: Intracellular Proteins As Targetmentioning

confidence: 99%

Functional nucleic acids for detecting bacteria

Huang

Liu²,

Liu³

2013

Reviews in Analytical Chemistry

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Bacterial infection represents one of the leading causes of disease and death, and as such, bacterial detection is an important step in managing infectious diseases. The current protocol requires growing cell cultures, which can take several days. Fast detection of low copies of bacterial cells has thus posed an analytical challenge. Among the new strategies developed to achieve this goal, functional nucleic acids (FNAs) have emerged to be a promising platform. FNAs include DNAzymes, aptamers, and aptazymes, all of which can recognize analytes other than complementary nucleic acids. FNAs are obtained using a combinatorial biology technique called systematic evolution of ligands by exponential enrichment (SELEX). FNAs have been isolated against not only purified proteins and surface markers from bacterial cells but also whole cells. A diverse range of signaling mechanisms including fluorescence, color, and electrochemistry-based detection has been reported. Although the majority of current sensors cannot achieve single-cell sensitivity, with improved combinatorial selection techniques and the incorporation of nanomaterials to realize multivalent binding and signal amplification, FNAs represent a feasible solution for bacterial detection.

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“…According to molecular Ambler classification, Carbapenem hydrolysing enzymes belong to classes A, B, D and are called as carbapenemases. The carbapenemases in class B require one or two zinc ions for their complete catalytic activity and are therefore called Metallo-betalactamases (MBLs) (Shlesinger et al, 2011). MBLs are considered to be more crucial than other mechanisms of the resistance as they can hydrolyse almost all beta-lactam antimicrobial agents.…”

Section: Introductionmentioning

confidence: 99%