“Sugar” Molecule in Cells Plays Crucial Role in Disease Prevention

The body’s inherent production of a specific sugar-based molecule plays a crucial role in various cellular functions, including growth, differentiation into different cell types, self-destruction if necessary, and more.

This molecule, known as poly (adenosine diphosphate ribose) or poly(ADP-ribose), not only safeguards the cell's genome and repairs DNA but also regulates the inheritance of genes. Unraveling the precise mechanisms of poly(ADP-ribose) could offer valuable insights for disease prevention and treatments.

In pursuit of a deeper understanding, researchers from Gifu University's Institute for Glyco-core Research (iGCORE) in Japan have created two synthetic versions of an ADP-ribose fragment.

The study was reported in the European Journal of Organic Chemistry on September 23^rd, 2023.

When cells engage in protein synthesis, they interpret genetic instructions to construct proteins. Throughout this process, certain molecules or molecular fragments can attach themselves to the protein, influencing post-translational modifications.

The poly(ADP-ribose) fragment, specifically the ribosyl adenosine 5′,5′′-diphosphate, could unveil distinct cellular functions. However, the natural variability of occurring fragments poses a challenge for scientists attempting to attribute comprehensive functions to them.

The problem is lack of the availability of homogeneous oligo- and poly(ADP-ribose) samples which are necessary for molecular-level studies to elucidate their detailed functions.”

Hide-Nori Tanaka, Study Co-Corresponding Author and Assistant Professor, iGCORE

Tanaka added, “To address this bottleneck and accelerate ADP-ribose biology, we developed two practical synthetic approaches to ribosyl adenosine 5',5"-diphosphate, a fragment of poly(ADP-ribose), for providing structurally well-defined ADP-ribose oligomer and polymer.”

Oligo- and poly(ADP-ribose) refers to the number of components that bind together to make up the ADP-ribose molecule.

The initial technique entailed a gradual assembly, utilizing a readily accessible solution to construct a framework.

Subsequently, researchers introduced carbohydrates to this framework. In contrast, the second method was simplified into a singular step. In this process, researchers worked with a known molecule, capable of binding to other molecules, extracted from a commercially available solution.

Both approaches yielded a shared precursor that transforms into a conjugation-ready building block, poised for integration in ADP-ribose synthesis, as outlined by Tanaka.

The next step is ADP-ribose oligomer synthesis using the building block we prepared in this paper. Our ultimate goal is to elucidate the detailed functions of oligo- and poly(ADP-ribose) by chemical biology approach using synthetic molecules.”

Hide-Nori Tanaka, Study Co-Corresponding Author and Assistant Professor, iGCORE