2'-SEME-MODIFIED OLIGONUCLEOTIDES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在这项工作中，我们希望进一步证明，硒的衍生化可以极大地方便物相的确定，并有助于拆分大分子的结构。由于硒策略极大地方便了蛋白质领域的结构测定，它也可以应用于核酸领域，这一点实际上已经被我们的实验室证明了。除了物相测定外，我们还发现，在某些序列中(不到1小时)，对晶体进行2‘位的硒修饰可以使晶体生长得比天然的快得多。这里有一个例子，我们在短时间内得到了这个含硒核酸序列(5‘-Gu(2’-Se)GTACAC-3‘)的晶体。因此，除了检查晶相测定方法以扩大其应用范围外，我们还希望从X射线结晶学中了解更多的结构细节，如水化规律和糖的堆积等，这将有助于解决核酸结构研究领域中的两个主要难点--结晶和相问题。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In this work, we would like to further prove that selenium derivatization can greatly facilitate the phase determination and help to resolve the structures of macromolecules. Since the selenium strategy have greatly facilitated the structure determination in the field of protein, it can also be used in nucleic acid field, which actually has been proved by our lab. Besides the phase determination,we also found that selenium modification at the 2' position can make the crystals grow much faster in some sequences(less than one hour~!)than native ones. Here is an example, we got the crystals for this selenium contained nucleic acid sequence (5'-GU(2'-Se)GTACAC-3') in a short time. So, in addition to check the phase determination to widen it's application, we also like to know more structural details from the X-ray crystallography, such as hydration pattern and sugar packing, etc. It will be helpful to solve the cryallization and phase problem, the two main difficulties in the field of nucleic acid structure study.