Aziridine Mediated Peptide Ligation

通过这一奖项，化学部化学合成计划资助华盛顿州立大学化学系的菲利普·加纳教授探索一种新的化学策略(氮杂环丙氨酸介导的多肽连接)的开发，用于连接未受保护的多肽片段并在连接部位修饰结果产物。这一两步反应始于在天然条件下，铜(II)促进的未保护多肽硫代酸和未保护氮杂环肽的化学选择性偶联，得到初始产物，其反应性氮杂环嵌在预定的位置。偶联反应之后是氮杂环丙烷开环反应，得到最终的连接产物。该项目将解决两个有待解决的重要化学连接问题：(1)需要开发更通用的多肽连接方法，以绕过天然化学连接的N-末端半胱氨酸要求；(2)需要化学连接方法，使在连接事件期间能够针对特定部位引入修饰。该项目产生的技术可能会影响生物、医学和纳米技术领域。该项目的教育部分将包括培训研究生和本科生研究人员，为他们在化学领域的学术或工业职业做准备。将努力从代表性不足的群体中招募学生参与这一项目。

With this award, the Chemical Synthesis Program of the Chemistry Division is funding Professor Philip Garner of the Department of Chemistry at Washington State University to explore the development of a new chemical strategy (aziridine mediated peptide ligation) for the union of unprotected peptide segments and modification of the resulting product at the ligation site. This two-stage process begins with the chemoselective Cu(II)-promoted coupling of an unprotected peptide thioacid and unprotected aziridinyl peptide under native conditions to give an initial product with a reactive aziridine ring embedded at a pre-determined site. The coupling reaction is followed by an aziridine ring-opening reaction to give the final ligation product. This project will address two important chemical ligation problems that remain to be solved: (1) the need to develop more general peptide ligation methodology that circumvents the N-terminal Cys requirement of native chemical ligation and (2) the need for chemical ligation methodology that enables the site-specific introduction of modifications during the ligation event. The technology resulting from this project could impact the fields of Biology, Medicine, and Nanotechnology. The educational component of this project will include training graduate students and undergraduate researchers, so as to prepare them for either academic or industrial careers in chemistry. An effort will be made to recruit students from underrepresented groups to work on this project.