Aziridine Mediated Peptide Ligation

有了这个奖项，化学部的化学合成项目资助了华盛顿州立大学化学系的Philip Garner教授，以探索一种新的化学策略（叠氮吡啶介导的肽连接）的发展，该策略用于将未受保护的肽段结合并在连接位点修饰最终产物。这一过程分为两个阶段，首先是Cu（II）促进的无保护肽硫酸和无保护氮基二酰肽在天然条件下的化学选择性偶联，以获得在预定位置嵌入活性氮基环的初始产物。偶联反应之后是一个氮化吡啶开环反应，得到最终的结扎产物。该项目将解决两个仍有待解决的重要化学连接问题：(1)需要开发更通用的肽连接方法，以绕过天然化学连接对n端Cys的要求；(2)需要化学连接方法，使在连接事件中能够在特定位点引入修饰。这个项目产生的技术可能会影响生物学、医学和纳米技术领域。这个项目的教育部分将包括培训研究生和本科生研究人员，使他们为化学的学术或工业生涯做好准备。将努力从代表性不足的群体中招募学生参与这个项目。

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.