ProFACT News

 

Small molecule modulation of protein function is the primary mechanism of action of drugs, and so new methods to assess drug promiscuity and non-specific toxicity are continuously evolving. While such methods are essential in the pre-clinical and discovery process, two critical deficiencies remain: 1) proteomic analyses for broadly relating and characterizing the kinetics of enzyme variants responsible for the disease phenotype, and 2) proteomic analyses to assess in vitro drug responsiveness based on enzyme kinetics from natural cellular sources such as from cell lines and tissue homogenates.

 

In this webinar, ProFACT describes advances in its proprietary functional proteomics platform – SeraFILE™, and related Conformerics™ prospecting strategies, for these purposes. We first will describe how we apply SeraFILE™, a novel proteomic separations and compartmentalization platform, to derive signature profiles of enzyme activity from different biological sources. Such profiles provide new and characteristic kinetic data which can be compared sample to sample, disease to non-disease, and tissue type to tissue type. Thus for biomarker discovery, these signature profiles help define a target set of observable differences in kinetic response to various in vitro stimuli of the active site – the variants, from those samples. The stimuli can come from drug candidates or competing substrates, and the variants potentially span the continuum of enzymatic sub-states generated by natural transient features and regulatory factors, post-translational modifications, amino-acid sequence (families, mutations), or splice variants.

 

We will also describe new products for Kinase and Phosphodiesterase enrichment and the DeepSee™ kit - a subset of the full SeraFILE™ platform that includes 6 different surface fractionation modalities. New strategies to prospect and enrich for functional biomarkers, and potentially identify responsive (and non-responsive) natural source enzyme(s) to a challenging inhibitor will be discussed.