Ducancel Frédéric
Biol Aujourdhui. 2016;210(2):89-99. doi: 10.1051/jbio/2016016. Epub 2016 Sep 30.
Animal venoms are complex chemical cocktails, comprising a wide range of biologically active reticulated peptides that target with high selectivity and efficacy a variety of enzymes, membrane receptors, ion channels...Venoms can therefore be seen as large natural libraries of biologically active molecules that are continuously selected and highly refined by the evolution process, up to the point where every molecule is endowed with pharmacological properties that are highly valuable in the context of human use and drug development. Therefore, venom exploration constitutes a prerequisite to drug discovery. However, mass spectrometry and transcriptomics via NGS (Next Generation Sequencing) studies have shown the presence of up to 1000 peptides in the venom of single species of cone snails and spiders. Therefore the global animal venom resource can be seen as a collection of more than 50 to 100 000 000 peptides and proteins of which only ~5000 are known. That extraordinary "Eldorado" of bio-optimized compounds justifies the development of more global and cutting-edge strategies and technologies to explore this resource more efficiently than actually. De novo developed approaches and recently obtained results will be described.
动物毒液是复杂的化学混合物,包含多种具有生物活性的网状肽,这些肽能以高选择性和高效性作用于多种酶、膜受体、离子通道……因此,毒液可被视为生物活性分子的大型天然库,它们在进化过程中不断被筛选并高度优化,直至每个分子都具备在人类应用和药物开发方面具有极高价值的药理特性。所以,毒液探索是药物发现的前提条件。然而,通过质谱分析和基于二代测序(NGS)的转录组学研究表明,单一种类的芋螺和蜘蛛毒液中存在多达1000种肽。因此,全球动物毒液资源可被视为由超过5000万至1亿种肽和蛋白质组成的集合,其中只有约5000种是已知的。这种生物优化化合物的非凡“黄金国”证明了开发更全面、前沿的策略和技术以比实际情况更高效地探索这一资源的合理性。将描述新开发的方法和最近取得的成果。