A supramolecular indicator displacement assay for acetyl amantadine, a proxy biomarker for spermidine/spermine N1-acetyltransferase (SSAT) activity
Introduction
Cancer is a leading cause of death worldwide.1 The number of new cancer cases is expected to increase 40% in the next 15 years in Canada due to an aging and growing population.2 Lung cancer is the most commonly diagnosed in this country (excluding nonmelanoma skin cancers) and accounts for 14% of all new cases of cancer. It is the leading cause of death from all cancers for both men and women in Canada and worldwide. Early detection of cancers can increase the chances for effective therapy and therefore the survival rate. Biomarker-based detection for lung cancer would be a highly desirable addition to the arsenal of early detection strategies.
Cancer biomarkers can be DNA, mRNA, proteins, or metabolites. Despite intensive research efforts, some cancer biomarkers remain too insensitive or nonspecific for effective cancer detection. As far as lung cancer detection is concerned, no molecular biomarkers for early stage cancers have been discovered that have clinical usefulness. Therefore, development of lung cancer biomarker analysis with good sensitivity, selectivity, and stability is urgently needed.
Polyamines (e.g., putrescine, spermidine, and spermine) play vital roles in both eukaryotic and prokaryotic cell growth, differentiation, ion channel activity, and other functions.9 Their metabolic pathways are highly regulated and their concentrations inside cells are rigorously controlled. Concentrations of polyamines in certain types of cancer cells are also elevated.10 Spermidine/spermine N1-acetyltransferase (SSAT) is an enzyme that carries out the spermidine/spermine acetylation reaction on the aminopropyl moieties in vivo.11 SSAT is a GCN5-related N-acetyltransferase (GNAT), which catalyzes the transfer of acyl groups from acetyl- CoA to primary amines of its substrates (Fig. 1A). SSAT is involved in the process of cellular polyamine degradation and removal.
