Our goal is to utilize olefin cross-metathesis to synthesize alkene-peptide isosteres. Isosteres are molecules that mimic the size and geometry of the targeted molecule but lack an electronic component (such as an H-Bond donor or acceptor). A useful isostere of the amide bond is a trans-alkene. Our initial target is the peptide sequence D-Ala-D-Ala, (present on bacterial cell walls). This peptide sequence is implicated in the recognition of Vancomycin (a potent antibiotic) to the bacteria. By replacing the amide bond with a trans-olefin, information about the nature of this interaction can be probed by asking, "How much is an H-bond worth?"

The D-Ala-D-Ala isostere target will allow us to develop convergent approaches to peptide-isostere synthesis that can be applied to any peptide target. Olefin cross metathesis will be used as the key reaction in formed in the trans-alkene.