Systematic development of novel peptide-derived inhibitors for methyl-regulatory enzymes

点击翻译按钮获取中文摘要

Through a direct partnership with Zim Corp. and their subsidiary Nuvobio, a local Ottawa-based company with interest in molecular tools and peptide inhibitors, this proposal will allow the partner organization to efficiently design and commercialize cell-active and target-specific inhibitors. The development of these commercialized resources will enable the broader study of protein function and the deconvolution of cellular processes. As protein dysfunction is commonly hallmarked as critical drivers of disease progression, Zim has recognized that there is an urgent need to develop strategies that can be used to study basic protein biology. As a result, there is a need for the development of tools that are necessary to study protein function in a cellular context. Through research enabled by our collaborative effort, we will be able to spark growth in novel, peptide-centric biotechnology products that will ultimately benefit Canadians and the Canadian economy. This initial collaborative work will focus on the generation of peptide-inhibitors for two classes of proteins that regulate a chemical protein modification referred to as lysine methylation, specifically, lysine methyltransferase (KMT) and demethylase (KDM) enzymes. Lysine methylation has emerged in the last decade as a protein modification with expanding implications in a number of cellular processes, and the dysfunction of several KMT and KDMs are known drivers of cancer. Given the involvement of Lys methylation in a growing number of different biological processes, perhaps it is not surprising that the study of methylation events has been increasingly important in understanding basic cellular biology. As a result, there is a great interest to understand the biology of these methyl-regulatory enzymes, however, only a handful of KMT and KDM inhibitors have been discovered or developed. This collaboration addresses this issue and represents a significant effort towards expanding the commercial market of KMT and KDM inhibitors. The goal of this proposed NSERC Alliance collaborative research program is to develop target-specific peptide inhibitors of KMT and KDM enzymes as tools for the study of the methyl-Lys proteome.