Protein chips offer the potential to profile the levels and kinetics of proteins in tissues of the digestive and endocrine systems in a highly multiplexed format. Despite this potential, the majority of protein chips are based on arrayed bio-molecules obtained from biologic or enzymatic sources. Chips that rely on biology or enzymes suffer from several inherent shortcomings that include a restricted bio-molecule repertoire that is time-consuming and costly to manufacture, especially at high-density. We propose to overcome these limitations by developing a Meta-Molding array technology that consists of arrays of novel synthetic antibody mimetics. Mimetics will be identified using a novel and purely chemical discovery paradigm termed PNAdisplay. Consistent with previous studies in the field of dynamic combinatorial chemistry, we hypothesize that PNA-display will permit us to screen large heterodimer populations and identify at least moderate affinity mimetics in a facile system (i. e. < 10 (M). Arrays of such moderate-affinity mimetics employed with an orthogonal analytical method such as MALDI-TOF will provide an analytical capability exceeding that of antibody arrays alone, but without the disadvantages. This SBIR Phase I proposal is designed to prove the feasibility of using PNA-display to identify at least moderate affinity mimetics. Feasibility will set the stage to move into an aggressive Phase II program to develop a Meta-Molding array that monitors global intracellular signaling by detecting specific phosphopeptides. Inappropriate intracellular phosphorylation results in several diseases, including cancer, non-insulin dependent diabetes, and peripheral neuropathies. Syntrix will commercialize the Meta-Molding arrays that result from this research through third-party joint ventures.
| Ye, Guofeng; Schuler, Aaron D; Ahmadibeni, Yousef et al. (2009) Synthesis and evaluation of phosphopeptides containing iminodiacetate groups as binding ligands of the Src SH2 domain. Bioorg Chem 37:133-42 |
