• 한국미생물·생명공학회지
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• 제16권5호
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• pp.398-401
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• 1988

$\beta$-lactamase을 저해하는 물질을 생성하는 방선균의 일균주를 토양에서 분리하였다. 분리된 균으로부터 $\beta$-lactamase 저해물질을 생산하는 조건을 검토하였고, 아울러 배양액에서부터 동 물질을 분리정제하여 그 특성의 일부를 조사하였다. 그 결과 이 물질은 $\beta$-lactam ring을 가지고 있지 않았으며, $\beta$-lactam 항생물질에 대한 내성을 나타내는 E. coli 내성균주에 강한 항생력을 나타냄을 알았다.

• KSBB Journal
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• 제6권1호
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• pp.111-114
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• 1991

대장균의 plasmid상의 ${\beta}-lactamase$를 IPTG induction으로 대량 생산할 때 precursor processing inhibitor (CCCP)를 가하여 ${\beta}-lactamase$의 soluble fraction과 insoluble fraction (inclusion body)의 생산성을 비교하였다. CCCP로 처리한 경우가 더 많은 soluble ${\beta}-lactamase$를 생성하였으나,inclusion body의 양에는 큰 차이가 없었다. 이것은 ${\beta}-lactamase$ precursor processing 속도를 낮출 경우 soluble ${\beta}-lactamase$가 더 많이 생성된다는 것을 보여주었다.

• Journal of Microbiology and Biotechnology
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• 제1권2호
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• pp.85-89
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• 1991

The aim of this study is to elucidate characteristics of ${\beta}-lactamase$ inhibitor produced by Streptomyces sp. SMF-19 isolated from soil was found to produce proteinaceous extracellular ${\beta}-lactamase$ inhibitor. The ${\beta}-lactamase$ inhibitor was purified through ammonium sulfate fractionation, gel filtration, anion exchange chromatography and fast performace liquid chromatography. The molecular weight of the ${\beta}-lactamase$ inhibitor was estimated to be about 48,000 by SDS-PAGE. The mode of inhibition against penicillin G as a substrate was uncompetitive. The ${\beta}-lactamase$ inhibitor was stable in wide pH range but unstable at high temperature above $50^{\circ}C$.

• 약학회지
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• 제41권5호
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• pp.658-665
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• 1997

Identification of a soil microorganism strain X-8, producer of ${\beta}$-lactamase inhibitor, based on its morphological, physiological, biochemical and chemotaxonomical characteristics was performed. The strain X-8 was identified as Pseudomonas sp. The beta-lactamase inhibitor produced by this strain was highly achieved in fermentation medium contained glucose 0.5%, urea 0.25%, $K_2HPO_4{\cdot}3H_2O\;0.5%,\;MgSO_4{\cdot}7H_2O\;0.5%,\;FeSO_4{\cdot}7H_2O\;0.01%,\;CuSO_4,\;ZnSO_4,\;MnSO_4\;0.02%$. The beta-lactamase inhibitor was not extracted by organic solvent such as n-butanol and ethyl acetate but remained in aqueous layer. The n-butanol extract showed antimicrobial activity against M. smegmatis. The ${\beta}$-lactamase inhibitor was stable at pH 7.0~8.0 and 4$^{\circ}C$ for 24h. The ${\beta}$-lactamase inhibitor was bound on ion exchanger Diaion WA-30 and HP-20 and eluted with 2N-$NH_4OH$ and acetone, respectively.

• 대한수의학회지
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• 제43권1호
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• pp.113-120
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• 2003

The antimicrobial effect of ${\beta}$-lactam antibiotics, which had ${\beta}$-lactamase inhibitor activity, on Staphylococcus aureus isolated from mastitis was investigated in this study. Out of 166 isolates, 99 isolates (59.6%) produced ${\beta}$-lactamase, and 98 isolates of 99 were ${\beta}$-lactamase positive in above $12.5{\mu}g/m{\ell}$ MIC of penicillin. In the providence distribution, ${\beta}$-lactamase production rate of 4 providence, Gangwon, Gyeonggi, Chungcheong, and Jeolla was 100%, 65.7%, 58.8%, and 50.0%, respectively. Antibiotic activities of ${\beta}$-lactam antibiotics against lactamase positive isolates also were investigated. Antimicrobial effects of ampicillin/sulbactam or amoxicillin/clavulanic acid treated group were better than ampicillin or amoxicillin treated group. In antimicrobial effects on intracellular S aureus, there was no difference 1 hour and 4 hour treatment in control, ampicillin, and amoxicillin group, but in 18 hours treatment, ampicillin/sulbactam or amoxicillin/clavulanic acid had a better effect than ampicillin or amoxicillin (p<0.05).

• 약학회지
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• 제51권6호
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• pp.447-454
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• 2007

The resistance of bacteria against ${\beta}$-lactam antibiotics is mainly caused by the production of ${\beta}$-lactamase enzymes. ${\beta}$-Lactamase inhibitors are used in combination with known antibiotics to overcome the growing problem of bacterial resistance. We prepared 6-(thienylmethylene)penam sulfones for the development of potent ${\beta}$-lactamase inhibitors and evaluated their ${\beta}$-lactamase inhibitory activities.

• Biomolecules & Therapeutics
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• 제14권4호
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• pp.220-225
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• 2006

Derivatives of penicillanic acid sulfones are known to be irreversible inhibitors of $\beta$-lactamase. Eight 6-tricyclic methylene penicillanic acid sulfones were prepared, and their $\beta$-lactamase inhibitory activities were evaluated against $\beta$-lactamase types I, II, III and IV. Among the tricycles attached to 6-exomethylenepenam sulfones, thiazolobenzimidazole(12a-12b), fluorene(12c), and carbazole(12e), showed inhibitory activity on type I, II and III $\beta$-lactamase. But phenanthrene(12d), and anthracene(12f-12h) derivatives showed little $\beta$-lactamase inhibitory activity. The synergic effects of the selected compound(l2b) in 1:4 combination with piperacillin showed some protection to piperacillin for the resistant strains of E. coli DC2 and P. aeruginosa 1771.

• 약학회지
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• 제52권4호
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• pp.311-315
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• 2008

The synthesis of 7-arylidene cephalosporanates for ${\beta}-lactamase$ inhibitor was described. The reactions of substituted benzyl halides $[1]{\sim}[3]$ with triphenylphosphine gave triphenylphcsphonium chlorides $[4]{\sim}[6]$. These phosphonium salts were treated with n-butyllithium to give ylides, which were reated with 7-oxocephalosporanate [7] by Wittig reaction to afford the 7-exomethylene cephalosporanates $[8]{\sim}[10]$. These cephalosporanates were oxidized to cephalosporanate sulfones $[11]{\sim}[13]$ with mCPBA. The deprotection of benzhydryl cephalosporanate $[8]{\sim}[13]$ with $AlCl_3$ and $NaHCO_{3}$ gave sodium salts of 7-arylidene cephalosporanates $[14]{\sim}[19]$.

• 대한화학회지
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• 제49권5호
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• pp.461-469
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• 2005

• Bulletin of the Korean Chemical Society
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• 제31권12호
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• pp.3644-3652
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• 2010

The metallo-$\beta$-lactamases ($M{\beta}Ls$) are clinically significant enzymes which readily hydrolyze most $\beta$-lactam antibiotics. Discovering potential inhibitors for the $M{\beta}Ls$ is an expensive, time consuming endeavor. Virtual screening can sieve out inhibitor candidates with incompatible features prior to synthesis, decreasing these costs. Using Autodock 4.0, the binding locations and energies of four previously-studied potential inhibitors and four additional compounds obtained from the National Cancer Institute (NCI) database were computationally calculated. Based on the docking models of these eight compounds, we then designed several hypothetical inhibitor structures, compounds A through F, and performed their respective docking experiments. The docking results for compound F showed that it binds to the zinc containing active sites with a lowest predicted binding energy of -6.70 kcal/mol, suggesting F is the most likely potential $M{\beta}L$ inhibitor.