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- You, Liwen, et al.
(författare)
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Comprehensive bioinformatic analysis of the specificity of human immunodeficiency virus type 1 protease.
- 2005
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Ingår i: J Virol. - Washington, DC : The American Society for Microbiology. - 0022-538X .- 1098-5514. ; 79:19, s. 12477-86
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Tidskriftsartikel (refereegranskat)abstract
- Rapidly developing viral resistance to licensed human immunodeficiency virus type 1 (HIV-1) protease inhibitors is an increasing problem in the treatment of HIV-infected individuals and AIDS patients. A rational design of more effective protease inhibitors and discovery of potential biological substrates for the HIV-1 protease require accurate models for protease cleavage specificity. In this study, several popular bioinformatic machine learning methods, including support vector machines and artificial neural networks, were used to analyze the specificity of the HIV-1 protease. A new, extensive data set (746 peptides that have been experimentally tested for cleavage by the HIV-1 protease) was compiled, and the data were used to construct different classifiers that predicted whether the protease would cleave a given peptide substrate or not. The best predictor was a nonlinear predictor using two physicochemical parameters (hydrophobicity, or alternatively polarity, and size) for the amino acids, indicating that these properties are the key features recognized by the HIV-1 protease. The present in silico study provides new and important insights into the workings of the HIV-1 protease at the molecular level, supporting the recent hypothesis that the protease primarily recognizes a conformation rather than a specific amino acid sequence. Furthermore, we demonstrate that the presence of 1 to 2 lysine residues near the cleavage site of octameric peptide substrates seems to prevent cleavage efficiently, suggesting that this positively charged amino acid plays an important role in hindering the activity of the HIV-1 protease.
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| 2. |
- Wen, Kangmei, et al.
(författare)
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Recent Research on Flavonoids and their Biomedical Applications
- 2021
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Ingår i: Current Medicinal Chemistry. - Sharjah : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 28:5, s. 1042-1066
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Forskningsöversikt (refereegranskat)abstract
- Flavonoids, commonly found in various plants, are a class of polyphenolic compounds having a basic structural unit of 2-phenylchromone. Flavonoid compounds have attracted much attention due to their wide biological applications. In order to facilitate further research on the biomedical application of flavonoids, we surveyed the literature published on the use of flavonoids in medicine during the past decade, documented the commonly found structures in natural flavonoids, and summarized their pharmacological activities as well as associated mechanisms of action against a variety of health disorders including chronic inflammation, cancer, cardiovascular complications and hypoglycemia. In this mini-review, we provide suggestions for further research on the biomedical applications of flavonoids. © Bentham Science Publishers
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| 3. |
- Johannesson, Petra, et al.
(författare)
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SAR and optimization of trioxoisothiazole-based liver receptor X (LXR) agonists leading to the clinical candidate AZD3971
- 2014
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Ingår i: Division of Medicinal Chemistry. ; , s. 247-247
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Konferensbidrag (refereegranskat)abstract
- The liver X receptors (LXRα and LXRβ) are members of the nuclear receptor family of transcription factors. The activation of LXR induces genes involved in reverse cholesterol transport (RCT), which is believed to be the main effect of LXR agonists in the prevention or treatment of atherosclerosis. However LXR agonists have also been shown to cause hepatic steatosis and hypertriglyceridaemia. The ability to separate beneficial effects from negative effects has been a challenge that so far has hampered the development of LXR agonists for human use. We herein describe the SAR and optimization of a series of trioxoisothiazole-based LXR agonists leading to compounds with nanomolar potencies and a separation of beneficial versus negative effects in vivo. This work ultimately led to the nomination of AZD3971 as a candidate for the treatment of atherosclerosis.
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