Design and Synthesis of Fluoroacylshikonin as an Anticancer Agent

A series of shikonin derivatives, selectively acylated by various fluorinated carboxylic acids at the side chain of shikonin, were synthesized and their anticancer activity evaluated, in which eight compounds are reported for the first time. Among all the compounds tested, compound S7 showed the most potent anticancer activity against B16‐F10 (malignant melanoma cells), MG63 (human osteosarcoma cells), and A549 (lung cancer cells) with IC₅₀ 0.39 ± 0.01, 0.72 ± 0.04 and 0.58 ± 0.02 µmol/L. Docking simulation of compound S7 was carried out to position S7 into a tubulin active site to determine the probable binding conformation. All the results suggested that compound S7 may be a potential anticancer agent. Chirality 25:757–762, 2013. © 2013 Wiley Periodicals, Inc.     

Differential Expression of Organic Acid Degradation-Related Genes During Fruit Development of Navel Oranges (Citrus sinensis) in Two Habitats

Organic acids as well as soluble sugars contribute highly to flavor and overall quality of citrus fruit. Citric acid level in fruit is influenced by several factors including environmental conditions. In this study, it was observed that different environments in two habitats (Ganzhou, Jiangxi; Songyang, Zhejiang) had minor effects on total soluble solids and citrus color index but had significant effects on organic acids levels, particularly on citric acid level, in fruit of “Newhall” and “SkaggsBonanza” navel oranges (Citrus sinensis). Expression of genes involved in citric acid biosynthesis and degradation (CitCS1, CitCS2, CitAco1, CitAco2, CitAco3, CitIDH1, CitIDH2, CitIDH3, CitGAD4, CitGAD5, and CitGS2) was analyzed in fruit grown in each of the two habitats. Citric acid biosynthesis-related citrate synthase genes were steadily expressed during navel orange fruit development, while degradation-related genes were differentially expressed. These findings suggested that the influence of different environments on fruit quality traits was predominant on the regulation of organic acids level, particularly on the degradation of citric acid. A cascade of CitAco3–CitIDH1–CitGS2 might be involved in citric acid degradation in response to different environments during fruit growth and development.     

Effect of Selective Substitution of 5-Bromocytosine on Conformation of DNA Triple Helices

Abstract

Three triplex DNAs containing 5-bromocytosine[^BrC] were studied by vibrational spectroscopy and molecular modelling. Firstly, three oligodeoxypyrimidines of 5′-(TC)3- T4-(^BrCT)3 [C^BrC], 5′-(T^BrC)3-T4-(CT)3 pCC] and 5′-(T^BC)3-T4-(^BrCT)3 [^BrC^BC] were synthesized and then reacted with an oligodeoxypurine of 5′-(AG)₃ at pH=4.5 in phosphate buffer respectively to form three comparative hairpin triplex named CY,YC and YY. The results of FT-Raman and IR revealed that YY is almost in A-like form, CY and YC are combinations of A-like form and B-like form, but A-form dominates in CY while B-form is equivalent as A-form in YC. The result is consistent with the theoretical analysis.     

Development of ETB Selective Agonists: Solution Structure of a Linear Endothelin-1 Analogue,ET-1 [Cys(Acm)1,15, Ala3, Leu7, dAsp8, Aib11]

Abstract

The solution structure of a synthetic ET_B selective agonist, ET-l[Cys(Acm)^1,15, Ala³, Leu⁷, dAsp⁸, Aib¹¹] has been solved by ¹H NMR and molecular modelling studies. Such solution structures of linear modified peptides in aqueous methanol are being used in an ongoing program of research designed to assist in an understanding of the basic structural requirements for the biological activity of vasoconstrictors. The resulting structure of this peptide is characterised by an α-helical conformation between residues Leu⁶-His¹⁶ and by N- and C-termi- ni which assume no defined conformation. A knowledge of the solution structures of this and related peptides, which are ETB selective agonists, are proving to be important in the understanding of how they interact with the ETB receptor.     

Overexpression of TaHSF3 in Transgenic Arabidopsis Enhances Tolerance to Extreme Temperatures

Heat shock factors (HSFs) in plants regulate heat stress response by mediating expression of a set of heat shock protein (HSP) genes. In the present study, we isolated a novel heat shock gene, TaHSF3, encoding a protein of 315 amino acids in wheat. Phylogenetic analysis showed that TaHSF3 belonged to HSF class B2. Subcellular localization analysis indicated that TaHSF3 localized in nuclei. TaHSF3 was highly expressed in wheat spikes and showed intermediate expression levels in roots, stems, and leaves under normal conditions. It was highly upregulated in wheat seedlings by heat and cold and to a lesser extent by drought and NaCl and ABA treatments. Overexpression of TaHSF3 in Arabidopsis enhanced tolerance to extreme temperatures. Frequency of survival of three TaHSF3 transgenic Arabidopsis lines was 75–91 % after heat treatment and 85–95 % after freezing treatment compared to 25 and 10 %, respectively, in wild-type plants (WT). Leaf chlorophyll contents of the transformants were higher (0.52–0.67 mg/g) than WT (0.35 mg/g) after heat treatment, and the relative electrical conductivities of the transformants after freezing treatment were lower (from 17.56 to 18.6 %) than those of WT (37.5 %). The TaHSF3 gene from wheat therefore confers tolerance to extreme temperatures in transgenic Arabidopsis by activating HSPs, such as HSP70.     

Recent progresses in gene delivery-based bone tissue engineering

Gene therapy has converged with bone engineering over the past decade, by which a variety of therapeutic genes have been delivered to stimulate bone repair. These genes can be administered via in vivo or ex vivo approach using either viral or nonviral vectors. This article reviews the fundamental aspects and recent progresses in the gene therapy-based bone engineering, with emphasis on the new genes, viral vectors and gene delivery approaches.