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  • By using the C elegans Matrisome

    2019-12-02

    By using the C. elegans Matrisome Annotator tool, we found substantial enrichment for matrisome Lisinopril dihydrate in these data sets. Thus, re-analyzing -omic datasets with the C. elegans Matrisome Annotator tool may be useful to generate novel hypotheses about the role of the C. elegans matrisome for various biological processes.
    Conclusions Defining proteins in cellular compartments has helped understand their functions and implication in various processes. The ECM has been implicated in many biological processes. Components of the ECM have essential roles for C. elegans development, cell migration, and aging. In this study, we defined the C. elegans matrisome, an ensemble of ECM proteins and associated factors. We identified conserved and nematode-specific components, which informs biomedical research and provides potential targets to fight pathogenic nematodes. The categorization and clustering of C. elegans collagens lays the foundation to experimentally test, for example, whether cuticular collagens might form heterotrimers. Using the C. elegans Matrisome Annotator tool, we found enrichment of ECM genes at the mRNA, protein, and phenotypic level. This will assist researchers in delineating genotype-to-phenotype relationships for ECM genes. Modern science is hypothesis-driven. We hope that our contribution in defining the C. elegans matrisome and providing tools to analyze -omic data will aid generating novel hypotheses to propel science forward. The following are the supplementary data related to this article.
    Introduction The Nuclear Hormone Receptor (NHR) superfamily of intracellular ligand-dependent transcription factors has historically been a rich source of targets for drug development, and compounds which selectively modulate gene-transcription through activation of these receptors have the potential to provide more favorable clinical profiles than those of the native hormones [1], [2], [3], [4]. In this regard, clinical use of the endogenous agonists of the Androgen Receptor (AR), testosterone and dihydrotestosterone, as well as related steroidal agents have demonstrated excellent anabolic efficacy in limited clinical trials. However, their use has been limited due to drawbacks associated with both the route of administration and concerns due to side-effects and toxicity of these steroidal agonists. In order to circumvent these liabilities, several groups have been actively engaged in the discovery and development of Selective Androgen Receptor Modulators (SARMs) [5], [6], [7], [8], [9]. The most advanced of these compounds has entered clinical trials for treatment of a variety of disorders, including muscle wasting from HIV, cancer chemotherapy, chronic renal failure, male hypogonadism, benign prostatic hyperplasia, functional decline in the aging male, as well as for osteoporosis and sexual dysfunction in both men and women [10], [11], [12], [13], [14], [15], [16]. SARMs as a class hold significant potential for achieving the beneficial anabolic and cognitive enhancing effects of classical pure agonist compounds, without the associated side-effects, by virtue of multiple mechanisms mediating gene- and tissue-selective action. Further exploration of structure–activity relationships (SAR) within BMS\'s previously described novel series of SARMs resulted in the discovery of a number of diverse scaffolds conferring potent and tissue-selective agonist activity both in vitro and in vivo [17], [18], [19], [20]. Subtle changes in ligand structure were found to induce profound pharmacology differences when studied in whole-cells and in rodents. BMS-564929 is a potential Selective Androgen Receptor Modulator under development as an anticancer agent. The synthesis of BMS-564929 [20], [21] requires a key chiral intermediate, cis-3-hydroxy-l-proline. This paper describes the construction, cloning and heterologous expression of the l-proline-3-hydroxylase in Escherichia coli and the development of a process for the conversion of l-proline to cis-3-hydroxy-l-proline (Scheme 1).