Professor, University of British Columbia
Peptides for Therapy and Imaging: From Tryptathionine-Stapled Peptide Toxins for Targeted Therapy to One-Step 18F-Labeling of Peptides for PET-Oncology
For therapeutic applications, ADCs are seeing a renewed interest due to
improved antibody chemistries and new cytotoxic payloads. Alpha-amanitin,
is a well-known peptide cytotoxin that inhibits RNA polymerase II thus
killing both growing and quiescent cells. Recently, antibody-amanitin
antibodies were found to be effective against pancreatic cancer in mice
while Herceptin-amanitin conjugates are entering clinical trials. For over
8 decades, the total synthesis of amanitin has remained an elusive
challenge. This year we completed the first total synthesis of amanitin –
how we accomplished this and what we learned will be discussed.
Key to PET imaging is the ability to work with F-18 fluoride, the only
scalable PET-isotope. Yet its application has posed considerable
challenges in terms of labeling large biomolecules for clinical
applications. To meet this challenge, we have developed a user-friendly
one-step approach to 18F-labeling based on the development of novel
organotrifluoroborate prosthetic groups. We have used this approach to
advance new radiotracers for unmet needs in cancer-specific imaging
agents. The application of this novel method and its outcome to produce
excellent preclinical PET images will be discussed.
David M. Perrin graduated from U.C. Berkeley, obtained a Ph.D. from U.C.
Los Angeles with David Sigman and did postdoctoral work in France with
Claude Helene. He has published extensively at the inteface of chemistry
and biology on chemically modified DNAzymes, heterocycles for recognizing
DNA, indole-crosslinked peptides and natural products, ribozymology, and
PET imaging agents. He has been a professor at UBC since 2000.