Spirobicyclic molecules are emerging as new “previleged” pharmacophoric structures with application to a diverse range of human disease states. With collaborators at ACRI and NRC-IIT, ARMRC and Mount Allison and UNB Chemistry departments, we are exploring spirocycles synthesized via intramolecular Janovsky σ-complexes with post-synthetic catalytic functional group manipulations. Initial work in this area has uncovered unique proton transfer behaviour for a series of spirohydantoins:

 

Photostability of fluorescent molecules is one of the missing keys to their reliable utilization in a range of biological applications. We are pursuing a novel class of compound that are very stable and highly fluorescent in liquid and solid states.

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A key collaborator for the development of this research is NRC-IIT.

 

Metabolomic profiling of cells, tissues and organs has been shown to be a predictive and diagnostic tool for disease discovery and monitoring. The mature and stable technology of NMR spectroscopy is a highly informative experimental platform when coupled with statistical analysis for new discoveries in disease management. Work at ACRI in collaboration with NRC-IIT and NRC-IMB is beginning to look at synthetic chemical mixture analysis and cell culture extracts with this non-destructive technique. It is proving to be a worthy partner to whole genome profiling as conducted by microarrays.

 

Many important signalling cascades involve direct protein-protein interactions. Typically, inhibition of these macromolecular contacts are inefficiently effected with standard small molecule drug therapy. However, larger molecules such as peptides have emerged as a tool for the study of these types of interaction. In an initial study with NRC-IMB and Dalhousie University, Faculty of Medicine(Dept. Microbiology & Immunology) we will explore peptide mapping, protease-resistant cationic peptoids (Poly(N-alkylglycines)) and cationic peptide-peptoid hybrids in breast cancer and leukemia. The recent acquisition of a microwave solid-phase synthesis instrument will hasten this research.

 

Through the Atlantic Microarray Facility at ACRI, Dr. Culf produces high quality DNA and protein microarrays using silicon pin technology. A recent grant has enabled us to develop and implement novel laser calibaration methods to enable the precise manufacture of spotted microarrays. To date we have fabricated the following synthetic DNA oligonucleotide 50-mer microarrays:

(i) 38K double-spotted DNA oligonucleotide whole genome, Human

(ii) 2.5K alternative splicing gene array for the apoptosis pathway, Human

(iii) CD44, PAX 5, GATA, TAS 50-mer probes.

(iv) Atlantic Salmon (for Canada DFO, Moncton). Quadruplicate spots, 16K.

(v) American Lobster (for Canada DFO, Moncton). Quadruplicate spots, 12K.

(vi) Halibut (for NRC-IMB, Genome Atlantic). Quadruplicate spots, 40K.