• 대한화학회지
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• 제50권3호
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• pp.269-271
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• 2006

• Archives of Pharmacal Research
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• 제20권6호
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• pp.579-585
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• 1997

To gain further insight into the mechanism of action of antiestrogens, we examined the interaction of antiestrogen with the estrogen receptor system and with estrogen- noncompetable antiestrogen binding sites. In addition to binding directly to the estrogen receptor, antiestrogens can be found associated with binding sites that are distinct from the estrogen receptor. In contrast to the restriction of estrogen receptors to estrogen target cells, such as those of uterus and mammary glands, antiestrogen binding sites are present in equal amounts in estrogen receptor-positive and -negative human breast cancer cell lines, such as MCF-7, T47D, and MDA-MB-231 that differ markedly in their sensitivity to antiestrogens. In order to gain greater insight into the role of these antiestrogen binding sites in the action of antiestrogens, we have examined the biopotency of different antiestrogens for the antiestrogen binding sites and that is CI628 > tamoxifen > trans-hydroxy tamoxifen > CI628M > H1285 > LY117018. This order of affinities does not parallel the affinity of these compounds for the estrogen receptor nor the potency of these compounds as antiestrogens. Indeed, compounds with high affinity for the estrogen receptor and greatest antiestrogenic potency have low affinities for these antiestrogen binding sites. Antiestrogenic potency correlates best with estrogen receptor affinity and not with affinity for antiestrogen binding sites. In summary, our findings suggested that interaction with the estrogen receptor is most likely the mechanism through which antiestrogens evoke their growth inhibitory effects.

• 대한화학회지
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• 제59권1호
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• pp.93-96
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• 2015

• KSBB Journal
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• 제21권4호
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• pp.279-285
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• 2006

본 연구에서는 trypsin을 모델 단백질로 하여 단백질 본연의 환성을 유지할 수 있는 고정화 방법을 찾기 위하여 공유결합방법과 친화력 결합방법을 이용하여 trypsin을 고정화 하였다. Streptavidin-biotin system을 이용한 고정화 방법은 bioactivity 유지측면에서 공유결합 방법보다 우수함을 확인하였다. 하지만 streptavidin-biotin system을 이용하였을 때 고정화 수율이 낮은 것은 해결해야 할 과제이다. 분자량이 다른 기질들(BAPNA, insulin, BSA)을 대상으로 고정화 trypsin의 부위 특이적 절단 특성을 분석한 결과 streptavidin-biotin에 의해 고정화된 trypsin이 절단효율도 높고 sequence coverage도 높은 것으로 확인되었다. 또한 공유결합된 trypsin은 견고한 분자구조를 나타낸 반면 streptavidin-biotin system으로 고정화된 trypsin은 유연성이 높은 것을 QCM-D를 이용하여 관찰할 수 있었다. 따라서 streptavidin-biotin system에 의한 고정화 방법에서 streptavidin-biotin 결합이 일종의 spacer arm 역할을 하면서 고정화된 trypsin의 분자유연성을 향상시켜 절단반응의 부위특이성과 절단수율을 향상시키는 것으로 판단되었다.

• Journal of Microbiology and Biotechnology
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• 제17권11호
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• pp.1848-1855
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• 2007

Antibacterial activity of essential oils (Tea tree, Chamomile, Eucalyptus) on Staphylococcus aureus growth was evaluated as well as the essential oil-loaded alginate beads. The binding interactions between the cell and the essential oils were measured using an optical biosensor. The antibacterial activity of the essential oils to the cell was evaluated with their binding interaction and affinity. The antibacterial activity appeared in the order of Tea Tree>Chamomile>Eucalyptus, in comparison of the inhibition effects of the cell growth to the essential oils. The association rate constant and affinity of the cell binding on Tea Tree essential oil were $5.0{\times}10^{-13}\;ml/(CFU{\cdot}s)$ and $5.0{\times}10^5\;ml/CFU$, respectively. The affinity of the cell binding on Tea Tree was about twice higher than those on the other essential oils. It might be possible that an effective antibacterial activity of Tea Tree essential oil was derived from its strong adhesive ability to the cell, more so than those of the other essential oils.

• Genomics & Informatics
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• 제13권2호
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• pp.45-52
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• 2015

Acute myeloid leukemia is a well characterized blood cancer in which the unnatural growth of immature white blood cell takes place, where several genes transcription is regulated by the micro RNAs (miRNAs). Argonaute (AGO) protein is a protein family that binds to the miRNAs and mRNA complex where a strong binding affinity is crucial for its RNA silencing function. By understanding pattern recognition between the miRNAs-mRNA complex and its binding affinity with AGO protein, one can decipher the regulation of a particular gene and develop suitable siRNA for the same in disease condition. In the current work, HOXA9 gene has been selected from literature, whose deregulation is well-established in acute myeloid leukemia. Four miRNAs (mir-145, mir-126, let-7a, and mir-196b) have been selected to target mRNA of HOXA9 (NCBI accession No. NM_152739.3). The binding interaction between mRNAs and mRNA of HOXA9 gene was studied computationally. From result, it was observed mir-145 has highest affinity for HOXA9 gene. Furthermore, the interaction between miRNAs-mRNA duplex of all chosen miRNAs are docked with AGO protein (PDB ID: 3F73, chain A) to study their interaction at molecular level through an in silico approach. The residual interaction and hydrogen bonding are inspected in Discovery Studio 3.5 suites. The current investigation throws light on understanding of AGO-assisted miRNA based gene silencing mechanism in HOXA9 gene associated in acute myeloid leukemia computationally.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2005년도 생물공학의 동향(XVII)
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• pp.728-729
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• 2005

• IMMUNE NETWORK
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• 제12권4호
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• pp.155-164
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• 2012

It is well established that blocking the interaction of EGFR with growth factors leads to the arrest of tumor growth, resulting in tumor cell death. ER414 is a human monoclonal antibody (mAb) derived by guided selection of the mouse mAb A13. The ER414 exhibited a ~17-fold lower affinity and, as a result, lower efficacy of inhibition of the EGF-mediated tyrosine phosphorylation of EGFR when compared with mAb A13 and cetuximab. We performed a stepwise in vitro affinity maturation to improve the affinity of ER414. We obtained a 3D model of ER414 to identify the amino acids in the CDRs that needed to be mutated. Clones were selected from the phage library with randomized amino acids in the CDRs and substitution of amino acids in the HCDR3 and LCDR1 of ER414 led to improved affinity. A clone, H3-14, with a ~20-fold increased affinity, was selected from the HCDR3 randomized library. Then three clones, ER2, ER78 and ER79, were selected from the LCDR1 randomized library based on the H3-14 but did not show further increased affinities compared to that of H3-14. Of the three, ER2 was chosen for further characterization due to its better expression than others. We successfully performed affinity maturation of ER414 and obtained antibodies with a similar affinity as cetuximab. And antibody from an affinity maturation inhibits the EGF-mediated tyrosine phosphorylation of EGFR in a manner similar to cetuximab.

• Bulletin of the Korean Chemical Society
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• 제28권6호
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• pp.1005-1009
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• 2007

Leukotriene B4 (LTB4) is a potent chemoattractant for leukocytes and considered to be an inflammatory mediator. Human BLT2 (hBLT2) is a low-affinity G-protein coupled receptor for LTB4 and mediates pertussis toxin-sensitive chemotactic cell movement. Here, we dissected the interaction between hBLT2 and G-protein alpha subunits using GST fusion proteins containing intracellular regions of hBLT2 and various Gα protein including Gα i1, Gα i2, Gα i3, Gα s1, Gα o1, and Gα z. Among the tested Gα subunits, Gα i3 showed the highest binding to the third intracellular loop region of hBLT2 with a dissociation constant (KD) of 5.0 × 10?6 M. These results suggest that Gα i3 has the highest affinity to hBLT2, and the third intracellular loop region of hBLT2 is the major component for the interaction with Gα i3.

• EDISON SW 활용 경진대회 논문집
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• 제5회(2016년)
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• pp.62-66
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• 2016

Tumor suppressor protein p53 loses its function upon binding with the HDM2 protein, and inhibiting the p53-HDM2 interaction is critical to suppress tumor cell growth. Recently, the cyclized helix-loop-helix peptide (cHLH) mimicking the ${\alpha}-helix$ part of the p53 protein has been designed and found to exhibit high binding affinity with HDM2. Here, we report the structural and thermodynamic characteristics of the bound complex of the cHLH peptide with the HDM2 protein. We performed molecular dynamics simulations to investigate the structural features of the cHLH peptide as well as its complex with the HDM2. The binding free energy calculation based on the integral equation theory was also executed to quantify the binding affinity for the cHLH/HDM2 complex and to understand the factors contributing to the binding affinity. We found a variety of factors for the helix stability of the cHLH peptide as well as in the complexation with the HDM2, which may provide an insight into the development of anti-cancer drug designs.