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The Organogermanium Compound Ge-132 Interacts with Nucleic Acid Components and Inhibits the Catalysis of Adenosine Substrate by Adenosine Deaminase

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Abstract

Poly-trans-[(2-carboxyethyl)germasesquioxane] (Ge-132) is a water-soluble organogermanium compound that exerts various physiological effects, including anti-inflammatory activity and pain relief. In water, Ge-132 is hydrolyzed to 3-(trihydroxygermyl)propanoic acid (THGP), which in turn is capable of interacting with cis-diol compounds through its trihydroxy group, indicating that this compound could also interact with diol-containing nucleic acid constituents. In this study, we evaluated the ability of THGP to interact with nucleosides or nucleotides via nuclear magnetic resonance (NMR) analysis. In addition, we evaluated the effect of added THGP on the enzymatic activity of adenosine deaminase (ADA) when using adenosine or 2′-deoxyadenosine as a substrate. In solution, THGP indeed formed complexes with nucleotides or nucleosides through their cis-diol group. Moreover, the ability of THGP to form complexes with nucleotides was influenced by the number of phosphate groups present on the ribose moiety. Notably, THGP also inhibited the catalysis of adenosine by ADA in a concentration-dependent manner. Thus, interactions between THGP and important biological nucleic acid constituents might be implicated in the physiological effects of Ge-132.

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Acknowledgements

The authors want to thank K. Sakamoto (Hirosaki University) for his invaluable advice concerning the enzyme assay. We also thank H. Maeda (Hirosaki University) for his constructive comments. We did not receive any external funding or grants in support of this research.

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Authors and Affiliations

  1. Asai Germanium Research Institute Co., Ltd., Suzuranoka, Hakodate, Hokkaido, 042-0958, Japan

    Yasuhiro Shimada, Katsuyuki Sato & Tomoya Takeda

  2. The United Graduate School of Agricultural Science, Iwate University, Ueda, Morioka, Iwate, 020-8550, Japan

    Yasuhiro Shimada & Yoshihiko Tokuji

  3. Cell Biology Laboratory, Graduate School of Agricultural Science, Tohoku University, Aoba-ku, Sendai, Miyagi, 980-8577, Japan

    Tomoya Takeda

  4. Department of Food Science, Obihiro University of Agriculture and Veterinary Medicine, Inada, Obihiro, Hokkaido, 080-8555, Japan

    Yoshihiko Tokuji

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  1. Yasuhiro Shimada
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Correspondence to Yasuhiro Shimada.

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Shimada, Y., Sato, K., Takeda, T. et al. The Organogermanium Compound Ge-132 Interacts with Nucleic Acid Components and Inhibits the Catalysis of Adenosine Substrate by Adenosine Deaminase. Biol Trace Elem Res 181, 164–172 (2018). https://doi.org/10.1007/s12011-017-1020-4

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  • DOI: https://doi.org/10.1007/s12011-017-1020-4

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