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      Natural products in modern life science

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          Abstract

          With a realistic threat against biodiversity in rain forests and in the sea, a sustainable use of natural products is becoming more and more important. Basic research directed against different organisms in Nature could reveal unexpected insights into fundamental biological mechanisms but also new pharmaceutical or biotechnological possibilities of more immediate use. Many different strategies have been used prospecting the biodiversity of Earth in the search for novel structure–activity relationships, which has resulted in important discoveries in drug development. However, we believe that the development of multidisciplinary incentives will be necessary for a future successful exploration of Nature. With this aim, one way would be a modernization and renewal of a venerable proven interdisciplinary science, Pharmacognosy, which represents an integrated way of studying biological systems. This has been demonstrated based on an explanatory model where the different parts of the model are explained by our ongoing research. Anti-inflammatory natural products have been discovered based on ethnopharmacological observations, marine sponges in cold water have resulted in substances with ecological impact, combinatory strategy of ecology and chemistry has revealed new insights into the biodiversity of fungi, in depth studies of cyclic peptides (cyclotides) has created new possibilities for engineering of bioactive peptides, development of new strategies using phylogeny and chemography has resulted in new possibilities for navigating chemical and biological space, and using bioinformatic tools for understanding of lateral gene transfer could provide potential drug targets. A multidisciplinary subject like Pharmacognosy, one of several scientific disciplines bridging biology and chemistry with medicine, has a strategic position for studies of complex scientific questions based on observations in Nature. Furthermore, natural product research based on intriguing scientific questions in Nature can be of value to increase the attraction for young students in modern life science.

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          Most cited references71

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          MRBAYES: Bayesian inference of phylogenetic trees.

          The program MRBAYES performs Bayesian inference of phylogeny using a variant of Markov chain Monte Carlo. MRBAYES, including the source code, documentation, sample data files, and an executable, is available at http://brahms.biology.rochester.edu/software.html.
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            The genome of the African trypanosome Trypanosoma brucei.

            African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including approximately 900 pseudogenes and approximately 1700 T. brucei-specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.
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              Virtual screening of chemical libraries.

              Virtual screening uses computer-based methods to discover new ligands on the basis of biological structures. Although widely heralded in the 1970s and 1980s, the technique has since struggled to meet its initial promise, and drug discovery remains dominated by empirical screening. Recent successes in predicting new ligands and their receptor-bound structures, and better rates of ligand discovery compared to empirical screening, have re-ignited interest in virtual screening, which is now widely used in drug discovery, albeit on a more limited scale than empirical screening.
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                Author and article information

                Contributors
                lars.bohlin@fkog.uu.se
                Journal
                Phytochem Rev
                Phytochemistry Reviews
                Springer Netherlands (Dordrecht )
                1568-7767
                1572-980X
                7 January 2010
                7 January 2010
                June 2010
                : 9
                : 2
                : 279-301
                Affiliations
                Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Box 574, 751 23 Uppsala, Sweden
                Article
                9160
                10.1007/s11101-009-9160-6
                2912726
                20700376
                7902b84c-5073-45a1-86a6-e7bdd7591649
                © The Author(s) 2010
                History
                : 11 October 2009
                : 17 November 2009
                Categories
                Article
                Custom metadata
                © Springer Science+Business Media B.V. 2010

                Biochemistry
                phylogeny,cyclotide,chemgps-np,cox-2,truffle,tuber,pharmacognosy,trypanosoma,chemical space,viola,geodia,lateral gene transfer

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