Natural products used as a chemical library for protein–protein interaction targeted drug discovery

Jin, Xuemei,Lee, Kyungro,Kim, Nam Hee,Kim, Hyun Sil,Yook, Jong In,Choi, Jiwon,No, Kyoung Tai Elsevier 2018 Journal of molecular graphics & modelling Vol.79 No.-

<P><B>Abstract</B></P> <P>Protein–protein interactions (PPIs), which are essential for cellular processes, have been recognized as attractive therapeutic targets. Therefore, the construction of a PPI-focused chemical library is an inevitable necessity for future drug discovery. Natural products have been used as traditional medicines to treat human diseases for millennia; in addition, their molecular scaffolds have been used in diverse approved drugs and drug candidates. The recent discovery of the ability of natural products to inhibit PPIs led us to use natural products as a chemical library for PPI-targeted drug discovery. In this study, we collected natural products (NPDB) from non-commercial and in-house databases to analyze their similarities to small-molecule PPI inhibitors (iPPIs) and FDA-approved drugs by using eight molecular descriptors. Then, we evaluated the distribution of NPDB and iPPIs in the chemical space, represented by the molecular fingerprint and molecular scaffolds, to identify the promising scaffolds, which could interfere with PPIs. To investigate the ability of natural products to inhibit PPI targets, molecular docking was used. Then, we predicted a set of high-potency natural products by using the iPPI-likeness score based on a docking score-weighted model. These selected natural products showed high binding affinities to the PPI target, namely XIAP, which were validated in an <I>in vitro</I> experiment. In addition, the natural products with novel scaffolds might provide a promising starting point for further medicinal chemistry developments. Overall, our study shows the potency of natural products in targeting PPIs, which might help in the design of a PPI-focused chemical library for future drug discovery.</P> <P><B>Highlights</B></P> <P> <UL> <LI> This paper provides <I>in silico</I> drug discovery strategy to identify natural products capable to inhibit the protein–protein interactions. </LI> <LI> The predicted PPI inhibitor-like natural products were validated in an in vitro experiment. </LI> <LI> The XIAP inhibitor LENP0044 could be used as a potent template for further chemical optimization. </LI> <LI> Natural products can be used as potent candidates in the design of a PPI-focused chemical library for drug discovery. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

2003년 국내 중증급성호흡기증후군 진료 현황 및 문제점 분석

이진수,김은실,정문현,백제중,정선화,안주희,최영화,이선희,고철우,김성범,김민자,박승철,기현균,송재훈,최상호,김양수,이상오,조용균,박영훈,정숙인,김연숙,이흥범,손창희,장성희,정희진,김우주 대한감염학회 2004 감염과 화학요법 Vol.36 No.3

목적 : 2002년 말 중국에서 SARS가 발생한 이후 국내에서도 2003년 10월까지 총 3명의 추정환자, 17명의 의심환자가 보고되었다. 향후 추가적인 SARS의 유행이 우려되는 상황에서, 그간의 SARS 환자 진료에 있어서의 실질적인 준비사항, 진료 현황 등에 대한 조사를 통해 문제점을 파악하여, 향후 더 나은 대비가 될 수 있도록 개선점을 제시하고자 하였다. 재료 및 방법 : SARS로 의심되는 환자를 진료 경험이 있는 병원의료진을 대상으로 2003년 10월에 설문조사를 실시하였다. 설문에는 SARS 환자 진료 시의 실질적인 조치, 진료 현황, 병실, 응급실 및 외래에서의 격리 시설과 준비사항, 보건당국의 관리와 지원에 관한 사항을 포함하였다. 결과 : 대상이 되는 22개 병원 중 17개(17/22, 77.2%) 병원이 설문에 응하였다. SARS 환자를 위한 격리실은 응급실, 외래, 일반병실 및 중환자실에서 각각 9개(9/17, 52.9%), 5개(5/17, 29.4%), 15개(15/16, 93.7%), 4개(4/16, 25%) 병원에서 음압처리가 되어있지 않은 일인실 혹은 다인실이 사용되었고, 1개(1/16, 6.3%) 병원에서만 일반병실에서 음압격리실이 운영되었다. 입원환자의 진찰 시 개인보호구의 착용은 거의 모든 의료기관에서 이루어졌다. 보건당국에서 SARS지정병원의 시설 등을 사전에 확인한 곳은 1곳(1/12, 8.3%)이였고, 14개 병원(14/15, 93.3%)에서는 보건당국에 의뢰한 검사결과를 통하 받지 못하였다. 결론 : 의료기관에서 SARS 환자용 격리실뿐만 아니라 기존의 격리실 설비 등이 미흡하였으며, 특히 중환자실 및 외래의 준비가 더욱 부족하였다. 보건당국의 의료기관에 대한 종합적인 지원이 부족하였고, 병원과의 원활한 연계가 잘 이루어지지 않았다. SARS 만이 아닌 격리를 필요로 하는 질환의 적절한 진료를 위해 향후 병원 시설의 정비와 정부차원에서의 보다 구체적이고 실질적인 대책마련이 필요하다. Background : There was an worldwide outbreak of the Severe Acute Respiratory Syndrome (SARS) originated from China in late 2002. During that period three cases of suspected SARS and 17 cases of probable SARS were reported in Korea. With the concerns about the reemergence of SARS-coV transmission, it is important to be prepared for any possibility. So, this study is aimed to analysis the past measures in managing SARS and propose the amendatory plans to improve the preparedness. Materials & Methods : Questionnaires were collected among clinicians with any experience in managing the probable or suspected SARS cases in Oct. 2003. 17 out of 22 hospitals responded to the questionnaire. The contents in the questionnaire were practical activities, personal equipments, response plans, isolation facilities in emergency centers, outpatient clinics, general wards and intensive care units, and relationship with the public health department. Results : The dedicated isolation rooms in emergency centers, outpatient clinics, general wards, and intensive care units were prepared in 9 (9/17, 52.9%), 5 (5/17, 29.4%), 15 (15/16, 93.7%), and 4 (4/16, 25.0%) hospitals, respectively. Except for one hospital that newly made negative pressure room for SARS, single or multi-bed rooms without airborne infection control were used in all the other hospitals. The personal precaution principles were kept quite well in general wards. Before the designation of SARS hospital by the public health department prior evalution to see if the hospital was suitable for managing SARS was conducted in only 1 (1/12, 8.3%) hospital. The results of laboratory diagnosis were reported back in 1 (1/15, 6.6%) hospital. Conclusions : The isolation facilities which can control airborne infection were almost deficient not only for SARS but also for other respiratory transmissible diseases. For the infection control of transmissible diseases including SARS, more investment is needed on medical facilities and comprehensive support from the public health department required.

소화기 Behcet병: 13예의 임상분석

정희원,유빈,문희범,이인철,김병식,박건춘,김진천 대한대장항문학회 1995 Annals of Coloproctolgy Vol.11 No.1

日本의 人文·社會科學 硏究動向 調査

李注衡,朴仁熙,韓點洙,金文基,朴晋泰 慶北大學校 1983 論文集 Vol.36 No.-

In January 1983, the writer visited a few universites in Japan to survey the recent trend of studies in cultural and social Sciences. At that time what I researched is as follows; In Japan, many a learned society has been organized and the research activities were very lively. Mass publication of scientific periodicals and prompt translation of foreign writings showed the maturity of scientific atmosphere. It true that their study of literature has been performed on the basis of positivism since 1930'. But now Structuralism which consider's literary works as one organic unity of parts became the main basis of literary studies. And, Learned Society of Educational Law has been organized in Japan. In consequence, the level of researches in educational law could be remarkably high. So, it is necessary for us to study the law of education. For, to make it better, we must know not only the universal principles of education but also specific ones derived from the peculiar characteristics of Korean education. At the same time, in Japan, Department of the Law of Industrial Administration was established in 14 universities including Japan University. And with the help of it, companies could improve the efficiency in dealing with judicial affairs related with industrial administration. So, to be a winner in the international trade competition, it is also required for us to study the judicial affairs of industrial administration.

한국인 턱뼈관의 형태

김희진,이승일,정인혁 대한해부학회 1997 Anatomy & Cell Biology Vol.30 No.2

한국인 턱끝구멍의 형태

김희진,이승일,정인혁 대한해부학회 1995 Anatomy & Cell Biology Vol.28 No.1

흰쥐의 원위콩팥단위내 칼슘결합단백질 (calbindin-D28k)에 관한 면역세포화학적 연구

김영희,김완영,김인범,한승호,오수자,차정호,김진 대한해부학회 1997 Anatomy & Cell Biology Vol.30 No.6

Low serum bilirubin level predicts the develop-ment of chronic kidney disease in patients with type 2 diabetes mellitus

( Kang Hee Ahn ),( Sang Soo Kim ),( Won Jin Kim ),( Jong Ho Kim ),( Yun Jeong Nam ),( Su Bin Park ),( Yun Kyung Jeon ),( Bo Hyun Kim ),( In Joo Kim ),( Yong Ki Kim ) 대한내과학회 2017 The Korean Journal of Internal Medicine Vol.32 No.5

Background/Aims: We evaluated whether serum bilirubin levels can predict the development of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T₂DM). Methods: This was a retrospective observational longitudinal study of patients presenting at the Pusan National University Hospital. A total of₃₄₉ patients with T₂DM and preserved kidney function (estimated glomerular filtration rate ≥ 60 mL/min/1.73 m²) were enrolled. The main outcome was the development of CKD stage 3 or greater. The patients were divided into four groups according to the quartiles of the total serum bilirubin levels at baseline. Results: The group with the lowest range of total serum bilirubin level (Q₁) showed the highest cumulative incidence of CKD stage 3 or greater than that of the other lower quartiles (Q₁ vs. Q₄; hazard ratio [HR], 6.75; 95% confidence in-terval [CI], 1.54 to 29.47; p = 0.011). In multivariate analysis, the risk of developing CKD stage 3 or greater was higher in the second lowest quartile of the serum bili-rubin level than that in the highest quartile of the serum bilirubin level (Q₂ vs. Q₄; HR, 9.36; 95% CI, 1.33 to 65.73; p = 0.024). In the normoalbuminuria subgroup (n = 236), multivariate analysis showed that the risk of developing CKD stage 3 or greater was higher in the lowest quartile of the serum bilirubin level than that in the highest quartile of the serum bilirubin level (Q1 vs. Q4; HR, 7.36; 95% CI, 1.24 to 35.82; p = 0.019). Conclusions: Serum bilirubin might be an early clinical marker for predicting the progression of CKD in patients with T₂DM and preserved renal function.

DYNAMIC RESPONSE OF CARBON NANOTUBES DISPERSED IN NEMATIC LIQUID CRYSTAL

YOUNG HEE LEE,SANG YOUN JEON,KYUNG AH PARK,IN-SU BAIK,SEOK JIN JEONG,SEOK HO JEONG,안계혁,SEUNG HEE LEE 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2007 NANO Vol.2 No.1

The alignment and dynamic response of carbon nanotubes (CNTs) in nematic liquid crystal (NLC) medium induced by strong electric field have been observed through polarizing optical microscope. Density-functional calculations suggest that LC molecule anchors helically to the CNT wall to enhance π-stacking with a binding energy of nearly -2.0 eV due to a considerable amount of charge transfer from LC molecule to CNT, resulting in the formation of excess charges and permanent dipole moment in CNTs. Under strong electric field, the motion of CNTs distorted the director of adjacent LC molecules. Our detailed analysis of dynamics revealed that the four-lobe textures in vertical cell and two vertical stripes in in-plane switching cell were strongly correlated, i.e., the side view of textures by the vertical motion of CNTs in vertical cell was similar to the textures in in-plane switching cell. Interestingly, the magnitude of textures in microscope was strongly dependent on the size of CNTs and theapplied field strength. The statistical size distribution of textures similar to that of CNTs provided information for the degree of dispersion of CNTs.

백서 중대뇌 동맥의 폐쇄에 따른 경색의 시간적 변화

정진명,정영섭,박인성,이상형,김현집,최길수,한대희 대한신경외과학회 1993 Journal of Korean neurosurgical society Vol.22 No.3

For the assessment of clinical management, for the confirmation of clinical findings, and also for the evaluation of new diagnostic techniques to determine the location as well as the extent of area of infarction on evolution in cerebral tissue is essential. Sequential evolution of infarction in 2% 2, 3, 5-triphenyltetrazolium hydrochloride(TTC) staining and its concomitant neurological changes were investigated in the rat following left middle cerebral artery occlusion(MCAO). In addition, the pathological evaluation was performed in the same coronal cut slice of each TTC staining. The results were : 1) In the TTC staining method, the cerebral infarction was not found in the 2 hour group rats, and appeared as white or pink color after 4 hours. 2) The size of infarction was significantly correlated with time of occlusion before sacrifice(p<0.05). The size increment was most obvious between 8 hour and 24 hour groups. 3) The time evolution of cerebral infarction was most prominent in the cerebral cortex, and was minimal in the basal ganglia which are supplied by the 'end artery'. 4) The cerebral infarction appeared first in the coronal cuts at the 4, 6, and 8㎜ from the frontal pole, which is the main territory of MCA. 5) The cerebral infarction, mainly presented in the 4, 6, and 8㎜ coronal cuts from the frontal pole, extended from the pyriform cortex to the fronto-parietal cortex. It also appeared at 2, 10㎜ coronal cuts from the frontal pole in 24 hour group. 6) The neurologic sign was not correlated to the time of MCAO and the size of infarction on evolution. Therefore, the prediction of location and size of area of infarction on evolution was impossible by the neurological status. 7) The histopathological change was detected as early as in 2 hours. However, hematoxylin and eosin(H & E) stained sections showed only subtle changes, such as small irregular areas of cortical spongiosis and neuronal shrinkage up to 8 hours. There was no significant difference between lesion areas of 2 hour and 8 hour groups. The pathological findings of 24 hour group rats was definite and appeared as a central area of coagulation necrosis and rare faction surrounded by a zone of peripheral spongiosis.