• Title/Summary/Keyword: Drug discovery

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Heat Shock Responses for Understanding Diseases of Protein Denaturation

  • Kim, Hee-Jung;Hwang, Na Rae;Lee, Kong-Joo
    • Molecules and Cells
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    • v.23 no.2
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    • pp.123-131
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    • 2007
  • Extracellular stresses induce heat shock response and render cells resistant to lethal stresses. Heat shock response involves induction of heat shock proteins (Hsps). Recently the roles of Hsps in neurodegenerative diseases and cancer are attracting increasing attention and have accelerated the study of heat shock response mechanism. This review focuses on the stress sensing steps, molecules involved in Hsps production, diseases related to Hsp malfunctions, and the potential of proteomics as a tool for understanding the complex signaling pathways relevant to these events.

The Structure-Based Three-Dimensional Pharmacophore Models for Arabidopsis thaliana HPPD inhibitors as Herbicide

  • Cho, Jae Eun;Kim, Jun Tae;Kim, Eunae;Ko, Young Kwan;Kang, Nam Sook
    • Bulletin of the Korean Chemical Society
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    • v.34 no.10
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    • pp.2909-2914
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    • 2013
  • p-Hydroxyphenylpyruvate dioxygenase (HPPD) is a potent herbicide target that is in current use. In this study, we developed a predictive pharmacophore model that uses known HPPD inhibitors based on a theoretically constructed HPPD homology model. The pharmacophore model derived from the three-dimensional (3D) structure of a target protein provides helpful information for analyzing protein-ligand interactions, leading to further improvement of the ligand binding affinity.

BIOPHARMACEUTIC PROPERTIES OF DRUGS: NEW TOOLS TO FACILITATE DRUG DISCOVERY AND DEVELOPMENT

  • Amidon, Gordon L.
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1997.04a
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    • pp.3-5
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    • 1997
  • Properties of a good drug include safety, efficacy, half-life and bioavailability. With the current approach to drug discovery based on receptor-based and cell-based screening methods, compounds are frequently moved into development with poor bioavailability. With low bioavailability, drug administration is typically limited to parenteral routes, thus limiting the potential wide-spread utility of these therapeutic agents. The first and most important factor limiting a drug's bioavailability is the intestinal membrane permeability which in turn determines the maximum fi:action of the dose administered that can be absorbed. We have recently utilized new intubation methods for performing permeability measurements in humans and establishing a fundamental human data base for correlating intestinal jejunal membrane permeabilities with permeabilities determined in other systems, e.g., animals, tissue culture, as well as physical chemical properties.

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A Short Review on the Application of Combining Molecular Docking and Molecular Dynamics Simulations in Field of Drug Discovery

  • Kothandan, Gugan;Ganapathy, Jagadeesan
    • Journal of Integrative Natural Science
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    • v.7 no.2
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    • pp.75-78
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    • 2014
  • Computer-aided drug design uses computational chemistry to discover, enhance, or study drugs and related biologically active molecules. It is now proved to be effective in reducing costs and speeding up drug discovery. In this short review, we discussed on the importance of combining molecular docking and molecular dynamics simulation methodologies. We also reviewed the importance of protein flexibility, refinement of docked complexes using molecular dynamics and the use of free energy calculations for the calculation of accurate binding energies has been reviewed.

Cytochrome P450 monooxygenase analysis in free-living and symbiotic microalgae Coccomyxa sp. C-169 and Chlorella sp. NC64A

  • Mthakathi, Ntsane Trevor;Kgosiemang, Ipeleng Kopano Rosinah;Chen, Wanping;Mohlatsane, Molikeng Eric;Mojahi, Thebeyapelo Jacob;Yu, Jae-Hyuk;Mashele, Samson Sitheni;Syed, Khajamohiddin
    • ALGAE
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    • v.30 no.3
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    • pp.233-239
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    • 2015
  • Microalgae research is gaining momentum because of their potential biotechnological applications, including the generation of biofuels. Genome sequencing analysis of two model microalgal species, polar free-living Coccomyxa sp. C-169 and symbiotic Chlorella sp. NC64A, revealed insights into the factors responsible for their lifestyle and unravelled biotechnologically valuable proteins. However, genome sequence analysis under-explored cytochrome P450 monooxygenases (P450s), heme-thiolate proteins ubiquitously present in species belonging to different biological kingdoms. In this study we performed genome data-mining, annotation and comparative analysis of P450s in these two model algal species. Sixty-nine P450s were found in two algal species. Coccomyxa sp. showed 40 P450s and Chlorella sp. showed 29 P450s in their genome. Sixty-eight P450s (>100 amino acid in length) were grouped into 32 P450 families and 46 P450 subfamilies. Among the P450 families, 27 P450 families were novel and not found in other biological kingdoms. The new P450 families are CYP745-CYP747, CYP845-CYP863, and CYP904-CYP908. Five P450 families, CYP51, CYP97, CYP710, CYP745, and CYP746, were commonly found between two algal species and 16 and 11 P450 families were unique to Coccomyxa sp. and Chlorella sp. Synteny analysis and gene-structure analysis revealed P450 duplications in both species. Functional analysis based on homolog P450s suggested that CYP51 and CYP710 family members are involved in membrane ergosterol biosynthesis. CYP55 and CYP97 family members are involved in nitric oxide reduction and biosynthesis of carotenoids. This is the first report on comparative analysis of P450s in the microalgal species Coccomyxa sp. C-169 and Chlorella sp. NC64A.

Molecular characterization and expression pattern of a novel Keratin-associated protein 11.1 gene in the Liaoning cashmere goat (Capra hircus)

  • Jin, Mei;Cao, Qian;Wang, Ruilong;Piao, Jun;Zhao, Fengqin;Piao, Jing'ai
    • Asian-Australasian Journal of Animal Sciences
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    • v.30 no.3
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    • pp.328-337
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    • 2017
  • Objective: An experiment was conducted to determine the relationship between the KAP11.1 and the regulation wool fineness. Methods: In previous work, we constructed a skin cDNA library and isolated a full-length cDNA clone termed KAP11.1. On this basis, we conducted a series of bioinformatics analysis. Tissue distribution of KAP11.1 mRNA was performed using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis. The expression of KAP11.1 mRNA in primary and secondary hair follicles was performed using real-time PCR (real-time polymerase chain reaction) analysis. The expression location of KAP11.1 mRNA in primary and secondary hair follicles was performed using in situ hybridization. Results: Bioinformatics analysis showed that KAP11.1 gene encodes a putative 158 amino acid protein that exhibited a high content of cysteine, serine, threonine, and valine and has a pubertal mammary gland) structural domain. Secondary structure prediction revealed a high proportion of random coils (76.73%). Semi-quantitative RT-PCR showed that KAP11.1 gene was expressed in heart, skin, and liver, but not expressed in spleen, lung and kidney. Real time PCR results showed that the expression of KAP11.1 has a higher expression in catagen than in anagen in the primary hair follicles. However, in the secondary hair follicles, KAP11.1 has a significantly higher expression in anagen than in catagen. Moreover, KAP11.1 gene has a strong expression in inner root sheath, hair matrix, and a lower expression in hair bulb. Conclusion: We conclude that KAP11.1 gene may play an important role in regulating the fiber diameter.

Preparation of Gold Coated Liposomes for CT Contrast Medium (CT 조영을 위한 금 코팅 리포솜의 제조)

  • Wee, Tae In;Jeon, Ye Won;Cho, Young Jae;Cho, Sung Keun;Ha, Jeung;Lee, Jeong Won;Cho, Sun Hang;Han, Hee Dong;Shin, Byung Cheol
    • Journal of the Korean Chemical Society
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    • v.57 no.5
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    • pp.634-639
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    • 2013
  • The use of medical imaging has been increased for diagnosis of cancer or vessel disease. Among the medical imaging, computed tomography (CT) is one of the popular methods, however, which should need administration of contrast medium. Therefore, we developed gold coated liposomes (GCL) as a contrast medium. To coat gold on the liposomal surface, positive charged liposomes was prepared and then negative $Au^-$ can coat on the liposomal surface by electronic interaction. The size of GCL was $154.8{\pm}9.2$ nm and surface charge was $27{\pm}3.2$ mV, respectively. The morphology of GCL was confirmed by electron microscopy (SEM) and transmission electron microscopy (TEM). The coating efficiency of gold was 18%. Chemical procedure for gold coating on liposomal surface was not toxic for cell cytotoxicity by MTT assay. Finally, we demonstrated attractive CT image for GCL. Taken together, the GCL would be useful for various vessel related disease as a contrast medium.

Gypenoside XVII protects against myocardial ischemia and reperfusion injury by inhibiting ER stress-induced mitochondrial injury

  • Yu, Yingli;Wang, Min;Chen, Rongchang;Sun, Xiao;Sun, Guibo;Sun, Xiaobo
    • Journal of Ginseng Research
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    • v.45 no.6
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    • pp.642-653
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    • 2021
  • Background: Effective strategies are dramatically needed to prevent and improve the recovery from myocardial ischemia and reperfusion (I/R) injury. Direct interactions between the mitochondria and endoplasmic reticulum (ER) during heart diseases have been recently investigated. This study was designed to explore the cardioprotective effects of gypenoside XVII (GP-17) against I/R injury. The roles of ER stress, mitochondrial injury, and their crosstalk within I/R injury and in GP-17einduced cardioprotection are also explored. Methods: Cardiac contractility function was recorded in Langendorff-perfused rat hearts. The effects of GP-17 on mitochondrial function including mitochondrial permeability transition pore opening, reactive oxygen species production, and respiratory function were determined using fluorescence detection kits on mitochondria isolated from the rat hearts. H9c2 cardiomyocytes were used to explore the effects of GP-17 on hypoxia/reoxygenation. Results: We found that GP-17 inhibits myocardial apoptosis, reduces cardiac dysfunction, and improves contractile recovery in rat hearts. Our results also demonstrate that apoptosis induced by I/R is predominantly mediated by ER stress and associated with mitochondrial injury. Moreover, the cardioprotective effects of GP-17 are controlled by the PI3K/AKT and P38 signaling pathways. Conclusion: GP-17 inhibits I/R-induced mitochondrial injury by delaying the onset of ER stress through the PI3K/AKT and P38 signaling pathways.