Inositol polyphosphates, diphosphoinositol polyphosphates and phosphatidylinositol polyphosphate lipids: Structure, synthesis, and development of probes for studying biological activity

Polyphosphorylated myo-inositol compounds, including the inositol polyphosphates (InsPs), diphosphoinositol polyphosphates (PP-InsPs), and phosphatidylinositol polyphosphates (PIP(n)s), represent key biomolecules that regulate a litany of critical biological processes. These compounds exist with myriad combinations of phosphorylation patterns, resulting in a complex network of interconverting signaling molecules that control different events. Due to the significance and intricate nature of this molecular family, the elucidation of biological roles has elicited substantial interest in both the biochemical and chemical communities. Within this broad effort, strategies employing chemical synthesis for the production of both natural products and chemically modified structures have proven advantageous for determining activities. Herein, we will discuss recent advancements in these efforts, including (i) a brief overview of structure and biological activity, (ii) current methods for the chemical synthesis of phosphorylated myo-inositols, (iii) strategies for the design of biologically active probe structures, and (iv) case studies in which synthetic probes have been applied to characterize biological properties.