Mechanism of the natural product moracin-O derived MO-460 and its targeting protein hnRNPA2B1 on HIF-1α inhibition

Soung, Nak-Kyun,Kim, Hye-Min,Asami, Yukihiro,Kim, Dong Hyun,Cho, Yangrae,Naik, Ravi,Jang, Yerin,Jang, Kusic,Han, Ho Jin,Ganipisetti, Srinivas Rao,Cha-Molstad, Hyunjoo,Hwang, Joonsung,Lee, Kyung Ho,Ko, Nature Publishing Group UK 2019 Experimental and molecular medicine Vol.51 No.2

<▼1><P>Hypoxia-inducible factor-1α (HIF-1α) mediates tumor cell adaptation to hypoxic conditions and is a potentially important anticancer therapeutic target. We previously developed a method for synthesizing a benzofuran-based natural product, (R)-(-)-moracin-O, and obtained a novel potent analog, MO-460 that suppresses the accumulation of HIF-1α in Hep3B cells. However, the molecular target and underlying mechanism of action of MO-460 remained unclear. In the current study, we identified heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) as a molecular target of MO-460. MO-460 inhibits the initiation of HIF-1α translation by binding to the C-terminal glycine-rich domain of hnRNPA2B1 and inhibiting its subsequent binding to the 3’-untranslated region of <I>HIF-1α</I> mRNA. Moreover, MO-460 suppresses HIF-1α protein synthesis under hypoxic conditions and induces the accumulation of stress granules. The data provided here suggest that hnRNPA2B1 serves as a crucial molecular target in hypoxia-induced tumor survival and thus offer an avenue for the development of novel anticancer therapies.</P></▼1><▼2><P><B>Cancer: How a plant metabolite analog suppresses tumor growth</B></P><P>A synthetic analog of a chemical found in fruit suppresses tumor growth by targeting an RNA-binding protein (hnRNPA2B1) and preventing the production of a pro-cancer regulatory factor. Nak-Kyun Soung from the Korea Research Institute of Bioscience and Biotechnology, Cheongju, South Korea, and coworkers built on their previous discovery that a compound derived from a medicinal plant metabolite can suppress the activity of hypoxia-inducible factor-1α (HIF-1α). This protein, which is involved in many aspects of cancer biology, is activated in the low-oxygen microenvironments found inside tumors. The researchers show that the compound binds to a protein that helps with the conversion of HIF-1α–encoding RNA transcripts into HIF-1α proteins. Liver cancer cells treated with the compound grew slowly and produced less HIF-1α under both normal and low-oxygen culture conditions, highlighting the potential of this anti-cancer strategy.</P></▼2>

SERS Analysis of Self-Assembled Monolayers of DNA Strands on Gold Surfaces

Jang, Nak-Han Korean Chemical Society 2010 Bulletin of the Korean Chemical Society Vol.31 No.1

Photochemical Kinetics of Maleic to Fumaric Acid on Silver Nanoparticle Surfaces

Jang, Nak-Han,Jeong, Dae-Hong,Suh, Jung-Sang Korean Chemical Society 2005 Bulletin of the Korean Chemical Society Vol.26 No.5

A visible photochemistry of maleic to fumaric acid adsorbed on silver nanoparticle surfaces was investigated as probed by SERS using a simple flow method. Photoisomerization of maleic to fumaric acid was consecutively observed in the condition of various flow rates, which varied the exposure time of laser beam. The sequential SERS spectra of maleic acid indicated that the photochemical isomerization and desorption took place simultaneously on silver nanoparticle surfaces as a function of laser fluency and wavelength. For 530.9nm laser line excitation, the rate constant coefficients were obtained with a = 5.9 $sec^{-1}$ mW for isomerization and b = 13.9 $sec^{-1}$ mW for desorption, which $k_1\;=\;aI^n\;and\;k_2\;=\;bI^m$. Both reactions were one photon process (n = 1, m = 1) of a visible light and relatively fast process whose decay time was in the range of milli-second for 50 mW laser power. The rate of photochemical reaction increased on going toward the blue and photodesorption was a dominant process. A simple flow method used in this study was very useful to study a relatively fast photochemical reaction of molecules adsorbed on silver nanoparticle surfaces.

The Coordination Chemistry of DNA Nucleosides on Gold Nanoparticles as a Probe by SERS

Jang, Nak-Han Korean Chemical Society 2002 Bulletin of the Korean Chemical Society Vol.23 No.12

The DNA nucleosides(dA, dC, dG, dT)bound to gold nanoparticles (~13 nm) in aqueous solution has been studied as a probe by the SERS and their coordination structures have been proposed on the basis of them. According to UV-Visible absorption of gold nanoparticles after modifying with DNA nucleosides, the rates of absorption of dA, dC, and dG were much faster than that of dT as monitored by the aggregation kinetics at 700 nm. These data indicated that the nucleosides dA, dC, and dG had a higher affinity for the gold nanoparticles surface than nucleoside dT. As the result of SERS spectra, the binding modes of each of the nucleosides on gold nanoparticles have been assigned. A dA binds to gold nanoparticles via a N(7) nitrogen atom of the imidazole ring, which the C(6)-$NH_2$ group also participates in the coordination process. In the case of dC, it binds to the gold surface via a N(3) nitrogen atom of the pyrimidine ring with a partial contribution from the oxygen of C(2)=O group. A coordination of dG to the gold surfaces is also proposed. Although the dG has the two different nitrogens of a pyrimidine ring and the amino group, the N(1) nitrogen atom of a pyrimidine ring has a higher affinity after the hydrogen migrates to the amino group. Conversely, dT binds via the oxygen of the C(4)=O group of the pyrimidine ring. Accordingly, these data suggest that the nitrogen atom of the imidazole or the pyrimidine ring in the DNA nucleosides will bind more fast to the gold nanoparticles surfaces than the oxygen atom of the carbonyl group.

Photochemical Kinetics of Maleic to Fumaric Acid on Silver Nanoparticle Surfaces

Nak Han Jang*,Dae Hong Jeong,Jung Sang Suh* 대한화학회 2005 Bulletin of the Korean Chemical Society Vol.26 No.5

A visible photochemistry of maleic to fumaric acid adsorbed on silver nanoparticle surfaces was investigated as probed by SERS using a simple flow method. Photoisomerization of maleic to fumaric acid was consecutively observed in the condition of various flow rates, which varied the exposure time of laser beam. The sequential SERS spectra of maleic acid indicated that the photochemical isomerization and desorption took place simultaneously on silver nanoparticle surfaces as a function of laser fluency and wavelength. For 530.9 nm laser line excitation, the rate constant coefficients were obtained with a = 5.9 sec1 mW for isomerization and b = 13.9 sec1 mW for desorption, which k1 = aIn and k2 = bIm. Both reactions were one photon process (n = 1, m = 1) of a visible light and relatively fast process whose decay time was in the range of milli-second for 50 mW laser power. The rate of photochemical reaction increased on going toward the blue and photodesorption was a dominant process. A simple flow method used in this study was very useful to study a relatively fast photochemical reaction of molecules adsorbed on silver nanoparticle surfaces.

SERS Analysis of Self-Assembled Monolayers of DNA Strands on Gold Surfaces

Nak Han Jang 대한화학회 2010 Bulletin of the Korean Chemical Society Vol.31 No.1

SERS Analysis of CMC on Gold-Assembled Micelle

Nak Han Jang* 대한화학회 2004 Bulletin of the Korean Chemical Society Vol.25 No.9

SERS Analysis of CMC on Gold-Assembled Micelle

Jang, Nak-Han Korean Chemical Society 2004 Bulletin of the Korean Chemical Society Vol.25 No.9

The micellization of dodecylpyridinum chloride (DPC) assembled on aqueous gold nanoparticles has been studied as a function of concentration using Surface-Enhanced Raman Scattering (SERS). At the low concentration, the strong SERS band of the benzene ring moiety was observed at 1025 $cm^{-1}$, and assigned to “trigonal ring breathing”. According to high concentration of DPC, a new strong band was also appeared at 1012 $cm^{-1}$, which was assigned to “totally symmetry ring breathing”. The difference of two spectra seems to ascribe to the geometry of polar head group, i.e., pyridinium cation. These geometry exist flat-down at low concentration, whereas standing-up or tilted geometry at high concentration. The critical micelle concentration (CMC) was first obtained from the ratio of intensities of the two bands related to the benzene ring moiety by vibrational spectroscopy, and was about 28 mM. After the CMC, the benzene ring moiety in the micelle state was more restricted than in monomer state because there is no more change of intensities at 1012 $cm^{-1}$. In addition, the size of gold-assembled micelle was estimated using light scattering and it was about 328.3 nm.

중학교 과학교과서의 한자 화학용어가 학생들의 화학개념 이해도에 미치는 영향 분석

장난한 ( Nak Han Jang ),류재욱 ( Jae Wook Lyu ) 경북대학교 과학교육연구소 2009 科學敎育硏究誌 Vol.33 No.2

제7차 교육 과정의 7학년 과학교과서에서 화학영역의 용어를 분석하고 한자 화학용어에 대해 한문 선택반과 비한문 선택반 학생들의 난이도와 이해도를 분석하였다. 7학년 과학교과서에서 한자용어의 비율은6차 교육 과정에 비하여 약간 줄어들었으나 여전히 70%가 넘게 높았다. 학생들은 추상적인 개념어를 주로 어려워했으며, 전문용어를 비전문 용어보다 어렵게 생각하고 구체어거나 일상적으로 많이 사용하는 용어를 쉽게 생각하였다. 학생들의 한자용어에 대한 이해도의 경향은 난이도와 대부분 일치하였다. 한자 화학용어에 대한 이해도는 한문 선택반 학생들이 높았으며, 쉽게 전환된 화학용어에 대해 비교군의 차이가 없었고 모두 한자 화학용어에 대한 이해도보다 크게 향상되었다. 따라서 한자용어를 한글로 전환하여 가능한 쉽고 익숙한 한글 위주의 국 한 혼용의 용어로 교과서가 쓰인다면 과학교과에 대한 이해도가 향상되리라고 생각된다. The purpose of this research was to analyze the chinese chemistry terminology in chemistry unit of 7th grade science textbooks in 7th curriculum and find relationship between student understanding and difficulty index for chinese preferred students and non-chinese preferred students. The chinese terminology in 7th curriculum was reduced less than that of 6th curriculum but still was over 70%. Students had difficulties in understanding of abstract terminologies and science terms but thought easily the concrete, common terminologies. The tendency of student understanding was similar to that of difficulty index. For chinese chemistry terminology, understanding of chinese preferred students was higher than that of non-chinese preferred students. For easily translated chemistry terminology, there was no significant difference but both were showed the improved understanding. Therefore student understanding should be improved in science if science textbooks would be written by easily translated chemistry terminology.

산,염기 적정에서 용액의 부피 변화에 대한 대학생들의 오개념 연구

장낙한 ( Nak Han Jang ) 경북대학교 과학교육연구소 2009 科學敎育硏究誌 Vol.33 No.2

부피 측정법을 이용하여 산·염기 적정 실험에서 중화점을 측정할 때, 나는 용액의 부피 변화에 대한 한국 대학생들의 개념을 조사하였다. 이 연구에 의하면, 대부분의 대학생들은 산·염기 적정 동안 중화반응에 의해 물이 생성되기 때문에 부피가 증가한다는 오개념을 갖고 있었다. 그러나 이것은 용액에 있는 염에 의한 효과를 무시한 것이기 때문에, 부피 변화를 설명하는데 충분하지 않다. HCl/NaOH 중화반응 동안 용액의 부피 증가를 설명하기 위해, 나는 생성된 NaCl의 부분 몰부피를 계산하였다. 실험 결과와 계산된 부분 몰부피를 비교할 때, 나는 부피 증가의 주요 효과는 HCl/NaOH 중화반응 동안 생성된 NaCl의 부분 몰부피 때문이라는 것을 밝혔다. 여기서 산·염기 중화 적정 동안 용액의 부피 변화에 대한 오개념을 줄이기 위해, 나는 부분 몰부피의 개념을 대학생들에게 도입하도록 제안한다. I investigated Korean college students` conception about the volume change of solution when they detected the equivalence point during acid/base titration experiment using method of volume measurement. According to this study, most college students had a misconception that the volume increment was due to the formation of water by neutralization during acid/base titration. However, this is not enough to explain the volume change, neglecting contribution of a salt in solution. I calculated the partial molar volume of NaCl formed to explain the volume increment of solution during HCl/NaOH neutralization. Comparing the result of experiment with the calculation of partial molar volume, I elucidated that the main effect of volume increment was due to the partial molar volume of NaCl formed during HCl/NaOH neutralization. Here I propose to introduce college students to the concept of partial molar volume of the salt formed to reduce misconception about the volume change of solution during acid/base neutralization.