Grant: Research Tools and Instruments

Training: My trainees learn to synthesize novel monomer amino acids, nucleosides, boronic acids and incorporate these groups into complex bioconjugates (peptides and oligonucleotides) that will be used for cancer detection, diagnosis and treatment. Trainees in collaborators lab's will purify peptides for metal-mediated catalysis and resolve racemic mixtures of novel amino acids.*Indispensable Equipment: an HPLC (high performance liquid chromatograph) with diode-array UV-vis and auto-sampling is essential to purify and demonstrate purity for publication. We must replace/upgrade an aging 13-year-old HPLC to enable my trainees in my lab to produce key molecules for research, in collaboration with PIs at B.C. Cancer Research Agency, UCLA, and at local companies, Zymeworks Inc. and Iprogen. Trainees acquire skills in synthetic organic, bioconjugate, radio- and biological chemistry as they develop novel probes to translate these novel constructs into applications for human health. Over the past 13 years, we have established a strong and diverse publication record along with several patents. Specifically, trainees work on: 1) a proprietary class of peptide-trifluoroborate conjugates for PET imaging; 2) synthetically modified DNAs for catalysis and target binding that depend on modified nucleoside triphosphates, and 3) the total synthesis of amanitin, a toxic peptide natural product and clickable analogs for antibody-drug conjugates. Hence an HPLC is as essential for my lab. *Required for Publication: In order to publish these results, an HPLC with detection hardware is absolutely required; chromatograms backed up by advanced software analysis based on diode-array multi-wavelength detection give confidence to collaborators for translation. Because we work with radioactive molecules (32P), safety regulations necessitate a dedicated HPLC within a lab like mine, that is licensed for radioisotope use. *Dependent Collaborations: In addition, increased funding from the CIHR and the CCSRI (which do not allow for major equipment purchases) fund an increased number of trainees, which in turn have placed severe constraints on the machine, which runs nearly 24/7 via autosampler. Collaborations with Paul Schaffer (Triumf), and Kuo-Shyan Lin (BC Cancer Research Centre), Laurel Schafer and Jason Hein (UBC Chemistry) place my lab as a hub for generating numerous molecules that interest other key players at UBC. Finally, my lab's productivity is now severely jeopardized by a 13-year old HPLC that routinely fails, requiring part replacements, in many cases on the used market since the model is so old that Agilent no longer makes all the parts. Outdated software will be threatened by the need to replace the computer that services the HPLC yet where the software is not compatible with the new Windows operating system. *Summary: a new HPLC is requested to support a highly productive and collaborative research program at the interface of chemistry and biology. *