• 한국자기공명학회논문지
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• 제22권4호
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• pp.125-131
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• 2018

Chemical shift perturbation (CSP) is a simple NMR technique for studying binding of a protein to various ligands. CSP is the only technique that can directly provide both a value for the dissociation constant and a binding site from the same set of measurements. To accurately analyze the CSP data, the exact binding mode such as multiple binding, should be carefully considered. In this review, we analyzed systematically the CSP data with multiple modes. This analysis might provide insight into the mechanism on how proteins selectively recognize their target ligands to achieve the biological function.

• Bulletin of the Korean Chemical Society
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• 제31권8호
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• pp.2265-2271
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• 2010

In this study, wormorm-like polymeric micelles were construted from poly(L-lactic acid)-b-poly(ethyelen glycol) (PLLA-b-PEG) block copolymers via worm-like (or cylindrical) self- assembly that consisted of a relatively long PLLA block ($M_n$ 7K Daltons) at the core and a relatively short PEG block ($M_n$ 2K Daltons) as the shell. Several cancer-targeting moieties (such as folate, cobalamin, and cyclic arginine-glycine-aspartic (RGD) peptide) were chemically coupled with the succinylated or maleimided PEG block of PLLA-b-PEG to act as a cancer cell-specific targeting ligand for breast cancer. The worm-like micelles with muplite cancer cell-specific ligands proved to be successful in recognizing different breast cancer cells at once. This has the potential to aid in cancer-specific drug delivery and to be used as an effective treatment for breast cancer.

• Genomics & Informatics
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• 제10권3호
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• pp.153-166
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• 2012

A variety of ligands differ in their capacity to bind the receptor, elicit gene expression, and modulate physiological responses. Such receptors include Toll-like receptors (TLRs), which recognize various patterns of pathogens and lead to primary innate immune activation against invaders, and G-protein coupled receptors (GPCRs), whose interaction with their cognate ligands activates heterotrimeric G proteins and regulates specific downstream effectors, including immuno-stimulating molecules. Once TLRs are activated, they lead to the expression of hundreds of genes together and bridge the arm of innate and adaptive immune responses. We characterized the gene expression profile of Toll-like receptor 4 (TLR4) in RAW 264.7 cells when it bound with its ligand, 2-keto-3-deoxyoctonate (KDO), the active part of lipopolysaccharide. In addition, to determine the network communications among the TLR, Janus kinase (JAK)/signal transducer and activator of transcription (STAT), and GPCR, we tested RAW 264.7 cells with KDO, interferon-${\beta}$, or cAMP analog 8-Br. The ligands were also administered as a pair of double and triple combinations.

• 대한화장품학회지
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• 제34권1호
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• pp.1-8
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• 2008

피부장벽을 포함한 표피층은 인체의 조직 가운데에서도 가장 역동적인 기관이다. 다시 말해서 끊임없이 새로운 표피세포의 형성, 분화 및 탈각과정이 반복되면서 표피항상성(epidermal homeostasis)을 유지한다. 표피항상성은 피부기능 가운데 가장 주요한 기능인 permeability barrier homeostasis의 확립으로 연결된다. Permeability barrier homeostasis는 각질층에서 이루어지며 이를 형성하고 유지하기 위해 매우 정교하게 조절되어야 한다. 표피항상성을 조절하는 핵심 조절인자로서 nuclear hormone receptor(NHR)가 중심에 있음이 최근 다양한 연구를 통해 입증되었다. 이들은 각질세포 특이적인 단백질, 즉, involucrin, loricrin 및 trans-glutaminase 1(TG 1) 등의 발현을 유전자 수준에서 조절할 뿐 아니라 표피 지질성분의 생합성을 증가시키는 등 피부장벽을 구성하는 brick 및 mortar의 생성과 유지에 핵심적 역할을 하는 것으로 알려졌다. NHR 가운데 peroxisome proliferator activator receptor(PPAR)와 liver X receptor(LXR)의 activator/ligands가 리놀레인산 등 지방산, leukotriene, prostanoid 및 oxygenated sterol 등이 지질대사과정에서 형성된 지질 종류인 까닭에 liposensor로도 알려지고 있다. 따라서 liposensor들을 비롯한 PPAR과 LXR activator/ligands들은 피부장벽기능이 저해된 아토피성 피부를 포함하여 건조피부를 관리하는 epidermotherapy의 수단으로서 잠재적 가능성이 있다고 생각된다.

• 통합자연과학논문집
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• 제5권1호
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• pp.22-26
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• 2012

Chemokine receptor antagonists have potential applications in field of drug discovery. Although the chemokine receptors are G-protein-coupled receptors, their cognate ligands are small proteins (8 to 12 kDa), and so inhibiting the ligand/receptor interaction has been challenging. In particular, CCR2 and CCR5 and their ligands have been implicated in the pathophysiology of a number of diseases, including rheumatoid arthritis and multiple sclerosis. Based on their roles in disease, they have been attractive targets for the pharmaceutical industry, targeting both CCR2 and CCR5 could be a useful strategy. Because of the importance of these receptors, providing information regarding the binding site is of prime importance. Herein, we report the comparison of CCR2 of CCR5 binding sites both sequentially as well as structurally. We also urged the importance of crucial residues in the binding site, to facilitate the development of dual antagonists targeting both the receptors. These results could also be useful for the design of novel and potent dual CCR2 and CCR5 antagonists using structure based drug design.

• Natural Product Sciences
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• 제25권3호
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• pp.215-221
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• 2019

Inflammation is the crucial biological process of immune system which acts as body's defense and protective response against the injuries or infection. However, the systemic inflammation devotes the adverse effects such as multiple inflammation associated diseases. One of the best ways to treat this entity is by blocking the tumor necrosis factor alpha ($TNF-{\alpha}$) and TNF-related apoptosis-inducing ligand (TRAIL) to avoid the proinflammation cytokines production. Thus, this study aims to evaluate the potency of Sambucus bioactive compounds as anti-inflammation through in silico approach. In order to assess that, molecular docking was performed to evaluate the interaction properties between the $TNF-{\alpha}$ or TRAIL with the ligands. The 2D structure of ligands were retrieved online via PubChem and the 3D protein modeling was done by using SWISS Model. The prediction results of the study showed that caffeic acid (-6.4 kcal/mol) and homovanillic acid (-6.6 kcal/mol) have the greatest binding affinity against the $TNF-{\alpha}$ and TRAIL respectively. This evidence suggests that caffeic acid and homovanillic acid may potent as anti-inflammatory agent against the inflammation associated diseases. Finally, this study needs further examination and evaluation to validate the potency of Sambucus bioactive compounds.

• IMMUNE NETWORK
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• 제13권5호
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• pp.184-193
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• 2013

Co-signaling molecules are surface glycoproteins that positively or negatively regulate the T cell response to antigen. Co-signaling ligands and receptors crosstalk between the surfaces of antigen-presenting cells (APCs) and T cells, and modulate the ultimate magnitude and quality of T cell receptor (TCR) signaling. In the past 10 years, the field of co-signaling research has been advanced by the understanding of underlying mechanisms of the immune modulation led by newly identified co-signaling molecules and the successful preclinical and clinical trials targeting co-inhibitory molecules called immune checkpoints in the treatment of autoimmune diseases and cancers. In this review, we briefly describe the characteristics of well-known B7 co-signaling family members regarding the expression, functions and therapeutic implications and to introduce newly identified B7 members such as B7-H5, B7-H6, and B7-H7.

• 한국고분자학회:학술대회논문집
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• 한국고분자학회 2006년도 IUPAC International Symposium on Advanced Polymers for Emerging Technologies
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• pp.265-265
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• 2006

Multivalent interactions, which are characterized by the simultaneous binding of multiple ligands on multiple receptors, are prevalent in biological system. We have shown that it is able to make a supramolecular aggregate coated with multiple functional molecules fairly easily by simply mixing one building block. In this particular example, a mannose-coated object was able to agglutinate bacterial cells with cognate binding partners through multivalent interactions. This kind of strategy can be applied in developing materials that can selectively remove pathogens. Supramolecular assembly of this type should be very useful in exploring multivalent biological interactions.

• IMMUNE NETWORK
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• 제14권2호
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• pp.67-72
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• 2014

The herpes virus entry mediator (HVEM) is a member of the tumor necrosis factor receptor superfamily (TNFRSF), and therefore it is also known as TNFRSF14 or CD270 (1,2). In recent years, we have focused on understanding HVEM function in the mucosa of the intestine, particularly on the role of HVEM in colitis pathogenesis, host defense and regulation of the microbiota (2-4). HVEM is an unusual TNF receptor because of its high expression levels in the gut epithelium, its capacity to bind ligands that are not members of the TNF super family, including immunoglobulin (Ig) superfamily members BTLA and CD160, and its bi-directional functionality, acting as a signaling receptor or as a ligand for the receptor BTLA. Clinically, Hvem recently was reported as an inflammatory bowel disease (IBD) risk gene as a result of genome wide association studies (5,6). This suggests HVEM could have a regulatory role influencing the regulation of epithelial barrier, host defense and the microbiota. Consistent with this, using mouse models, we have revealed how HVEM is involved in colitis pathogenesis, mucosal host defense and epithelial immunity (3,7). Although further studies are needed, our results provide the fundamental basis for understanding why Hvem is an IBD risk gene, and they confirm that HVEM is a mucosal gatekeeper with multiple regulatory functions in the mucosa.

• Journal of Biosystems Engineering
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• 제39권2호
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• pp.111-114
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• 2014

Purpose: This review aims to introduce aptamers and the methods of its development to improve the sensitivity and selectivity to target bacteria. In this review, we have highlighted current developments and directions in the pathogen detection based on aptamers. Background: Aptamers, the specific nucleic acid sequences, can bind to targets with high affinity and specificity. Some of researches on the use of aptamers for the detection of pathogen have been reported in recent years. Aptamers have more applicability than antibodies for the development of pathogen detection using biosensor; such as easy to synthesis and labeling, lack of immunogenicity, and a low cost of production. However, only few reports on the development and use of aptamers for the detection of pathogen have been published. Review: Aptamers specific to pathogen are obtained by whole-cell systematic evolution of ligands by exponential enrichment (SELEX) process. SELEX process is composed of screening random oligonucleotide bound with target cells, multiple separation and amplification of nucleic acids, final identification of the best sequences. For improving those affinity and selectivity to target bacteria, optimization of multiple separating process to remove unbounded oligonucleotides from aptamer candidates and sorting process by flow cytometry are required.