• YAKHAK HOEJI
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• v.41 no.5
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• pp.615-621
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• 1997

Dehydropeptidase-I (DHP-I) was solubilized from porcine kidney by treatment with n-butanol and partially purified 19.25 fold by $(NH_4)_2SO_4$ precipitation, DEAE-Sepharose CL-6B ion exchange chromatography and Sephacryl S-300 HR chromatography with an overall yield of 19.16. DHP-I showed its optimal activity at pH 7.5 and 25$^{\circ}C$. Its activity was stable under neutral and alkaline conditions, but was disappeared under acidic condition. And DHP-I was heat-labile and its activity remained at 45$^{\circ}C$ for 3hrs. The enzyme was not inhibited by dicationic ions, while its activity was increased by $Co^{2+}$(1mM) and $Zn^{2+}$ (0.1mM). The enzyme was inhibited by EDTA and N-ethylmaleimide. The relative molecular mass of DHP-I was estimated to be approximately 100kDa by gel filtration chromatography. The $K_m$ value of DHP-I for glycyldehydrophenylalanine (GDHP) was 1.98mM. DWP20418 [(1R, 5S, 6S)-6-[1-(R)-Hydroxyethyl]-1-methyl-2-[(2S, 4S)-2-(piperazinylcarbonyl)-1-(R)-hydroxyethyl)pyrrolidine-4-thio]carbapen-2-em-3-carboxylic acid], compared with meropenem (MEPM), was rather easily hydrolized by DHP-I, while it was four times more resistant than imipenem (IPM) to DHP-I.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.238-238
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• 1996

각종 동물 및 인체 신장 유래 DHP-I에 의한 DA-1131, imipenem(IPM) 및 meropenem(MEPM)의 속도 상수를 측정한 결과, DA-1131은 동물종에 관계없이 가장 안정성이 큰 결과를 나타내었고, 인체 DHP-I에 대한 Vmax/Km 값이 IPM의 21.9%로 관찰되어 IPM보다 하위 기질인 것으로 확인되었다. DA-1131, IPM/CS 및 MEPM/CS의 20mg/kg투여 후의 혈중농도 반감기(T$_{1}$2/)는 각각 11.4분, 8.9분, 10.3분이었으며, 1$\mu\textrm{g}$/$m\ell$ 이상의 혈중농도룰 유지하는 시간은 66.6 분, 55.9 분, 63.1 분이었다. DA-1131, DA-l131/CS, IPM/CS, MEPM 및 MEPM/CS의 40 mg/kg 투여 후 24시간 동안의 뇨중 배설율은 57.9 %, 61.3%, 22.6 %, 11.3% 및 65.9%이었으며, 각 약물을 40 mg/kg 투여 15분 후 DA-ll3l의 폐중 농도는 11.2$\mu\textrm{g}$/g으로 DA-l131/CS, IPM/CS 및 MEPM/CS와 비슷한 결과를 나타내었으며 T/P ratio도 DA-1131, DA-l131/CS, IPM/CS 와 MEPM/CS 투여군에서 거의 동일한 것으로 확인되었다. 신장중 농도는 DA-1131 과 DA-l131/CS의 경우 29.l$\mu\textrm{g}$/g 및 34.2$\mu\textrm{g}$/g으로 큰 차이를 나타내지 않았으나, IPM/CS, MEPM 및 MEPM/CS 투여군에 비하여는 높은 결과로 나타났고 T/P ratio도 DA-1131과 DA-l131/CS 투여군이 IPM/CS, MEPM 및 MEPM/CS 투여군보다 놓은 것으로 확인되었다.

• YAKHAK HOEJI
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• v.39 no.3
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• pp.215-222
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• 1995

The in vitro antibacterial activities of new carbapenem. CRB 529, 535, 538, 545 and 550 with meropenem and imipenem were compared. CRB 529. 535, 538, 545 and 550 proved to have a broad an tibacterial spectrum. Its in vitro activity against standard 20 strains was almost the same as that of imipenem and slightly higher than that of meropenem. However. against clinical isolated P. aeruginosa, CRB 529, 535, 538, 545 and 550 showed significantly higher activity than imipenem, and also CRB 529, 535, 538, 545 and 550 showed almost the same activity than imipenem and meropenem against 82 clinical isolated strains including S. aureus (MRSA), S. aureus (MSSA), E. faecalis, E. facium, E. coli, P. aeruginosa, K. pneumonia, P. mirabiris, P. stuartii, M. morganii, C. freundii, E. cloacae, S. marcescens and A. calcoaceticus var. anitratus. The stability of CRB 529, 535, 538, 545 and 550 against porcine renal dehydropeptidase-I(DHP-1) was 10 folds higher than that of imipenem and was 3 folds higher than that of meropenem.

• Bulletin of the Korean Chemical Society
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• v.27 no.8
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• pp.1164-1170
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• 2006

The synthesis of a new series of 1$\beta$-methylcarbapenems having 5-($\alpha,\beta$-disubstituted ethyl)pyrrolidine moiety is described. Their in vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of substituents on the pyrrolidine ring was investigated. A particular compound (VIh) having $\alpha$-hydroxy-$\beta$-piperazinylethyl substituted moiety showed the most potent activity.