Organic Synthesis, Chemical Properties, and Biological Activities of Cyclic bis(3'-5')Diguanylic Acid (c-di-GMP) and Its Analogs

• Hyodo Mamoru

  名古屋大学大学院人間情報学研究科物質・生命情報学専攻

• Hayakawa Yoshihiro

  Graduate School of Human Informatics/Information Science, CREST/JST, Nagoya University

• Karaolis David K. R.

Bibliographic Information

Other Title

• 環状ビス（３′‐５′）ジグアニル酸（ｃ‐ｄｉ‐ＧＭＰ）および類縁体の有機合成，化学的性質，および生物活性
• カンジョウ ビス 3 5 ジグアニルサン c di GMP オヨビ ルイエンタイ ノ ユウキ ゴウセイ カガクテキ セイシツ オヨビ セイブツ カッセイ

Abstract

This paper describes efficient synthesis, chemical behaviors, and biological activities of cyclic bis (3'-5') diguanylic acid (c-di-GMP) and its analogs, including cyclic bis (3'-5') guanylic-inosinic acid (c-GpIp), cyclic bis (3'-5') guanylic-adenylic acid (c-GpAp), and bis (3'-5') diguanylic acid monophosphorothioate (c-GpGps). c-di-GMP was synthesized via two methods shown in Scheme 1 and Scheme 2. Between the two methods, that shown in Scheme 2 is more effective, particularly, for large-scale (gram-scale) synthesis to obtain the target compound in a high yield. While, c-GpIp, c-GpAp, and c-GpGps were synthesized via strategies similar to that of Scheme 2. Studies on chemical behaviors of c-di-GMP indicated that these cyclic dinucleotides exist as the monomers in aprotic solvents such as DMSO. By contrast, it was shown that c-di-GMP smoothly aggregates to form a mixture of many compounds in water, in < 0.9% sodium chloride solutions, in < 100 mM phosphate buffer solutions, and in < 100 mM ammonium acetate buffer solutions. All aggregated compounds smoothly revert to a single compound (probably an aggeregate) by dissolving in a 0.9% sodium chloride solution (a physiological salt solution), a > 100 mM phosphate buffer solution, or a > 100 mM ammonium acetate buffer solution. Biological investigation dis-closed some novel activities of c-di-GMP, such as inhibition of biofilm formation of Staphylococcus aureus, inhibition of basal and growth factor stimulated human colon cancer cell prolifelation, and reduction of the viluence of biofilm-formed Staphylococcus aureus in a mouse model.

Journal

• Journal of Synthetic Organic Chemistry, Japan

  Journal of Synthetic Organic Chemistry, Japan 64 (4), 359-370, 2006

  The Society of Synthetic Organic Chemistry, Japan

Keywords

• c-di-GMP
• nucleotide
• biofilm
• phosphoramidite
• aggregation
• cancer
• MRSA

Details

• CRID: 1390282680287749120
• NII Article ID: 10018131558
• NII Book ID: AN0024521X
• DOI: 10.5059/yukigoseikyokaishi.64.359
• ISSN: 18836526
• ISSN: 00379980
• NDL BIB ID: 7921735
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I7921735
• Text Lang: ja
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed