Daniel Jacques H
Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique, Rue de la Terrasse, 91198 Gif-sur-Yvette, France.
Curr Genet. 2008 Jun;53(6):373-9. doi: 10.1007/s00294-008-0195-9. Epub 2008 May 14.
Although invaluable for biology and medicine, general methods for the selection of inhibitors directed against any protein activity are still missing. To test whether the fitness-based interferential genetics (FIG) approach performed in yeast might contribute to changing this situation, we used this method for the selection of artificial-gene-encoded peptides targeted at firefly luciferase, a foreign protein which was expressed in yeast. Some of these peptides were shown to inhibit the light-producing activity of luciferase in vitro. These results obtained within a totally artificial setting provide a direct demonstration of FIG selection for antagonistic components. Moreover, they open the way for FIG as a simple and general approach for selecting peptides against any specific protein activity expressed in a cellular environment, thus yielding compounds of potential scientific, medical and therapeutic value. Conditions for the development of such valuable compounds in the future using FIG are discussed.
尽管对生物学和医学来说非常宝贵，但针对任何蛋白质活性的抑制剂选择通用方法仍然缺失。为了测试在酵母中进行的基于适应性的干扰遗传学（FIG）方法是否可能有助于改变这种情况，我们使用该方法来筛选靶向萤火虫荧光素酶的人工基因编码肽，萤火虫荧光素酶是一种在酵母中表达的外源蛋白。其中一些肽在体外显示出抑制荧光素酶发光活性的作用。在完全人工的环境中获得的这些结果直接证明了FIG可用于筛选拮抗成分。此外，它们为FIG作为一种简单通用的方法开辟了道路，该方法可用于筛选针对细胞环境中表达的任何特定蛋白质活性的肽，从而产生具有潜在科学、医学和治疗价值的化合物。文中还讨论了未来使用FIG开发此类有价值化合物的条件。
