• 약학회지
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• 제41권5호
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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.

• 약학회지
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• 제39권3호
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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.

• Animal cells and systems
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• 제7권4호
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• pp.309-315
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• 2003

Renal dipeptidase (RDPase, membrane dipeptidase, dehydropeptidase 1, EC 3.4.13.19) has been widely studied since it was first purified from porcine kidney brush border membrane. It was reported that RDPase activity in urine samples of acute and chronic renal failure patients decreases. Nitric oxide (NO) is a highly reactive free radical involved in a number of physiological and pathological processes. NO is able to act in a dual mode, leading either to induction of apoptosis or to blunted execution of programmed cell death. NO inhibited the RDPase release from porcine renal proximal tubules, which could be blocked by L-NAME. Chitosan, the linear polymer of D-glucosamine in $\beta$(1\longrightarrow4) linkage, not only reversed the decreased RDPase release by NO but also increased NO production in the proximal tubule cells. The stimulatory effect of NO on RDPase release from proximal tubules in the presence of chitosan must be different from the previously proposed mechanism of RDPase release via NO signaling pathway. Chitosan stimulated the RDPase release in the proximal tubules and increased RDPase activity to 220% and 250% at 0.1% and 1%, respectively. RDPase release was decreased to about 40% in the injured proximal tubules and was recovered in proportion to the increase of chitosan. Chitosan may be useful in recovery of renal function from $HgCl_2$injury.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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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.

• 한국미생물·생명공학회지
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• 제34권4호
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• pp.352-356
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• 2006

CW-270031, an injectable carbapenem, is a novel synthesized pyrrolidinyl-thio carbapenems. It was evaluated for its in vitro antibacterial activities in comparison with those of imipenem and meropenem against standard strains and clinical isolated strains, CW-270031 was more active than imipenem against gram-negative (E. coli and Klebsiella oxytoca) clinical isolates, but it was slightly active than meropenem. Against Klebsiella aeruginosa CW-118 MIC were 0.048 $\mu$g/ml for CW-270031, 0.19 $\mu$g/ml for imipenem. Against clinical E. coli MIC range were 0.012$\sim$0.195 $\mu$g/ml for CW-270031, 0.097$\sim$0.39 $\mu$g/ml for imipenem. Against clinical Klebsiella oxytoca MIC$_{50}$ were 0.09 $\mu$g/ml for CW-270031, 0.39 $\mu$g/ml for imipenem. Against gram-positive standard strains and clinical CW-270031 was slightly more activity than meropenem, but CW-270033 was less active than imipenem against these tested isolates. The subcutaneous injection of CW-270031 in mice revealed that the half-life of CW-270031 in serum was about 13 min, long than that of meropenem (10.6 min). CW-270031. was stable to hydrolysis by dog renal dehydropeptidase I (DHP-l) enzyme, to an more stabilities shown by meropenem.

• 한국식품영양과학회지
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• 제34권7호
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• pp.968-972
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• 2005

기능성 식품소재로서 이미 많이 알려진 키토산이 신장과 관련하여 식품이나 의료용 소재로서 활용이 가능한 지를 알아보기 위하여 신장 기능과 민감하게 관련이 있는 효소인 RDPase, Udpase의 활성을 체내$\cdot$체외 실험을 통하여 관찰하였다. 체외 실험에서 글리세롤에 의해 유도된 RDPase의 유리$\cdot$활성 감소를 다시 회복시키는 것을 관찰하였다. 체내실험에서 글리세롤 투여에 의하여 손상된 신장의 근위세뇨관에서 급격히 증가한 RDPase의 활성을 키토산이 확실하게 감소시키는 것을 관찰할 수 있었다. 키토산을 공급한 쥐의 소변에서의 Udpase의 활성이 증가하는 것을 관찰하였다.