The inositol pyrophosphate messengers (PP-IPs) have captured the attention of chemists and biologists, because of their unique chemical structure and their ability to mediate a plethora of remarkable phenotypes. Genetic perturbation of PP-IP biosynthesis in mice revealed a central role for these molecules in insulin secretion, age and diet-induced obesity, and fertility in males. While these phenotypes attest to the importance of these messengers, the underlying molecular mechanisms have remained enigmatic.Our lab is developing chemical tools to decipher the molecular details of PP-IP signaling.  I will report on our progress towards 1) Identifying PP-IP protein binding-partners, 2) Developing strategies to detect pyrophosphorylated proteins, and 3) Perturbing PP-IP biosynthesis with pharmacological agents.Using these tools, we plan to elucidate how PP-IPs can intersect with processes that regulate the development of complex pathologies, such as diabetes and obesity. Financial support from the NIH (R00GM087306) is gratefully acknowledged.

Decoding inositol pyrophosphate signaling using chemical tools

245th National Meeting (2013)

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