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.
