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Project abstract for group distefan
Analysis and Engineering of Prenyltransferases
Protein prenyltransferases catalyze the addition of C15 or C20 isoprenoid groups to a variety of proteins. Because many proteins involved in signal transduction processes contain this modification, considerable interest exists in understanding the chemistry and biology of this phenomenon. Of particular note is the observation that protein prenylation is required for the transforming activity of mutant Ras oncoproteins; inhibition of the enzyme farnesyltransferase (which catalyzes protein prenylation) arrests the growth of transformed cells in a variety of in vivo models. A number of inhibitors of this enzyme are currently in clinical trials for cancer therapy and other diseases. This group's work in this area is focused in two broad directions. First, they are performing mutational analysis of prenyltransferases with the goal of understanding how they recognize their substrates for medical applications and engineering them to accept chemically modified substrates for biotechnology applications. A second area is in the development of two-photon removable protecting groups for application in the creation of photoactivatable drugs.
A bibliography of this group’s publications acknowledging MSI is attached.