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산성 인지질 이중층의 열적 상전이에 미치는 칼슘과 페노치아진 유도체의 영향
김남홍,노승배 大韓藥理學會 1990 대한약리학잡지 Vol.26 No.1
Dipalmitoyl phosphatidylcholine(DPPC)과 dipalmitoyl phosphatidic acid(DPPA) 리포좀내 이중층의 열적 상전이에 미치는 칼슘과 페노치아진 유도체의 영향을 시차 열량 분석계로 연구하였다. 인지질 이중층은 가열시 어느 특정온도에서 급격한 구조적 변화를 가져왔다. 이러한 온도에 의존한 변화는 순수 인지질의 경우 특이할 만큼 예민하였다. 순수 인지질에 페노치아진 유도체를 가하였을 때 순수 인지질의 상전이 온도보다 낮은 온도에서 일어 났으며 상전이 열그림을 넓적하게 만들었다. 칼슘 이온은 DPPC: DPPA(34: 66mol%)의 상전이 온도를 높였다. 그러나 위의 혼합 인지질에 페노치아진 유도체를 가하였을 때 <TEX>$73^{\circ}C$</TEX>에서의 작고 넓적한 곡선 부분이 사라졌다. 이러한 현상은 아마도 칼슘과 폐노치아진 유도체의 산성 인지질의 친수부분에서 상호 경쟁적 작용에 기인된 것으로 추정되어진다. The effects of phenothiazine derivatives and calcium on the thermotropic phase transition of bilayers in dipalmitoyl phosphatidylcholine (DPPC) and dipalmitoyl phosphatidic acid (DPPA) liposomes were investigated with differential scanning calorimeter (DSC). Bilayers underwent an abrupt organizational changes at a characteristic temperature when heated. Such temperature-dependent transition was particularly striking and sharp in the bilayers prepared from pure phospholipids. The ability of phenothiazine derivatives to modify the phase transition of phospholipids liposomes was measured by a broadening of the phase transition profile, that transition began to appear at lower temperature than which occurs in untreated liposomes. Calcium ion caused a large upward shift in the transition temperature of DPPC:DPPA (34:66mol%) liposomes. When the liposomes were first incubated with calcium ion followed by phenothiazine derivatives, disappearance of the broad curve centering at <TEX>$73^{\circ}C$</TEX> indicated displacement of calcium ion by phenothiazine derivatives at the anionic site. It is supposed that calcium ion and phenothiazine derivatives might compete with each other on the head group of acidic phospholipid.
Novel synthetic antibacterial agent, isosorbide-dinorfloxacin
김남홍,이종완,김영민,김은지,정재은,박성철,정갑산,박영훈,장미경 한국공업화학회 2015 한국공업화학회 연구논문 초록집 Vol.2015 No.0
Isosorbide was derived from renewable resources of cereal-based polysaccharides, has approved by FDA as GRAS (generally recognized as safe) materials. Norfloxacin is a synthetic antibacterial agent with broad-spectrum and has been used to treat for the complicated urinary tract infections. However, the poor water solubility of norfloxacin is a limiting factor in the bioavailability. In this study, we synthesized isosorbide-dinorfloxacin (ISDN) prodrug, that carboxyl groups of norfloxacin were conjugated with hydroxyl groups of isosorbide via esterification by lipase, resulted in the significantly enhanced water solubility and the showing antibacterial activity that was similar to free norfloxacin in drug-susceptible bacteria, interestingly, was enhanced in drug-resistance bacteria. (R0004115)
Mechanism action of α-helical peptides in drug-resistant bacteria
김남홍,김영민,김은지,정재은,박영훈,장미경,박성철 한국공업화학회 2015 한국공업화학회 연구논문 초록집 Vol.2015 No.0
Antibiotic-resistant bacteria have been increased due to abuse and misuse of antibiotics in biomedical fields. Therefore, to overcome that, many researchers have been finding new antibiotics. In present study, we designed eight antibacterial peptides. Present study was designed a series of synthetic α-helical peptides with amphiphilicity. They were composed of recurring (XWZX)n-NH2 sequences where X: cationic amino acids, W: tryptophan, Z:hydrophobic amino acids, n: number of repeat units. We analyzed action of eight antimicrobial peptides in drug-resistant bacteria of Pseudomonas aeruginosa and Staphylococcus aureus. The finding in the present study are able to provide basic information on design of effective antibiotic peptides. **This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded the Ministry of Education, Science and Technology (2013R1A1A4A01010701).
김남홍,노승배,Kim, Nam-Hong,Roh, Sung-Bae The Korean Society of Pharmacology 1990 대한약리학잡지 Vol.26 No.1
Dipalmitoyl phosphatidylcholine(DPPC)과 dipalmitoyl phosphatidic acid(DPPA) 리포좀내 이중층의 열적 상전이에 미치는 칼슘과 페노치아진 유도체의 영향을 시차 열량 분석계로 연구하였다. 인지질 이중층은 가열시 어느 특정온도에서 급격한 구조적 변화를 가져왔다. 이러한 온도에 의존한 변화는 순수 인지질의 경우 특이할 만큼 예민하였다. 순수 인지질에 페노치아진 유도체를 가하였을 때 순수 인지질의 상전이 온도보다 낮은 온도에서 일어 났으며 상전이 열그림을 넓적하게 만들었다. 칼슘 이온은 DPPC: DPPA(34: 66mol%)의 상전이 온도를 높였다. 그러나 위의 혼합 인지질에 페노치아진 유도체를 가하였을 때 $73^{\circ}C$에서의 작고 넓적한 곡선 부분이 사라졌다. 이러한 현상은 아마도 칼슘과 폐노치아진 유도체의 산성 인지질의 친수부분에서 상호 경쟁적 작용에 기인된 것으로 추정되어진다. The effects of phenothiazine derivatives and calcium on the thermotropic phase transition of bilayers in dipalmitoyl phosphatidylcholine (DPPC) and dipalmitoyl phosphatidic acid (DPPA) liposomes were investigated with differential scanning calorimeter (DSC). Bilayers underwent an abrupt organizational changes at a characteristic temperature when heated. Such temperature-dependent transition was particularly striking and sharp in the bilayers prepared from pure phospholipids. The ability of phenothiazine derivatives to modify the phase transition of phospholipids liposomes was measured by a broadening of the phase transition profile, that transition began to appear at lower temperature than which occurs in untreated liposomes. Calcium ion caused a large upward shift in the transition temperature of DPPC:DPPA (34:66mol%) liposomes. When the liposomes were first incubated with calcium ion followed by phenothiazine derivatives, disappearance of the broad curve centering at $73^{\circ}C$ indicated displacement of calcium ion by phenothiazine derivatives at the anionic site. It is supposed that calcium ion and phenothiazine derivatives might compete with each other on the head group of acidic phospholipid.