New Approach for the Synthesis of c-di-GMP and Its Analogues

Amiot, Nicolas; Heintz, Karine; Giese, Bernd

doi:10.1055/s-2006-950361

Cited by 7 publications

(1 citation statement)

References 24 publications

(37 reference statements)

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“…This stepwise synthesis of one CDN or its analogue takes more than 10 steps to generate one target molecule. Alternatively, CDN and its analogues have been prepared by directly glycosylating the macrocyclic ribose–phosphodiester backbone . However, there are a few natural nucleobases with uncommon protection groups for this procedure.…”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of Cyclic Dinucleotide Analogues Containing Triazolyl C-Nucleosides

Ma,

Xu,

Hou

et al. 2024

J. Org. Chem.

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Natural cyclic dinucleotide (CDN) is the secondary messenger involved in bacterial hemostasis, human innate immunity, and bacterial antiphage immunity. Synthetic CDN and its analogues are key molecular probes and potential immunotherapeutic agents. Several CDN analogues are under clinical research for antitumor immunotherapy. A myriad of synthetic methods have been developed and reported for the preparation of CDN and its analogues. However, most of the protocols require multiple steps, and only one CDN or its analogue is prepared at a time. In this study, a strategy based on a macrocyclic ribose phosphate skeleton containing a 1′-alkynyl group was designed and developed to prepare CDN analogues containing triazolyl C-nucleosides by click chemistry. Combinatorial application of click chemistry and the sulfenylation cascade to the macrocyclic skeleton expanded the diversity of the CDN analogues. This macrocyclic skeleton strategy rapidly and efficiently provides CDN analogues to facilitate research on microbiology, immunology, and immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Design and Synthesis of Cyclic Dinucleotide Analogues Containing Triazolyl C-Nucleosides

Ma,

Xu,

Hou

et al. 2024

J. Org. Chem.

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The Chemistry of the Noncanonical Cyclic Dinucleotide 2′3′-cGAMP and Its Analogs

Schwede

Genieser

Rentsch

2015

Non-Canonical Cyclic Nucleotides

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The cyclic dinucleotides (CDNs) cyclic diguanosine monophosphate (c-diGMP) and cyclic diadenosine monophosphate (c-diAMP) with two canonical 3'→5' internucleotide linkages are ubiquitous second messenger molecules in bacteria, regulating a multitude of physiological processes. Recently the noncanonical CDN cyclic guanosine monophosphate-adenosine monophosphate (2'3'-cGAMP) featuring a mixed linkage, which consists of a 2'→5' and a 3'→5' internucleotide bond, has been identified as a signaling molecule in metazoan species in late 2012. 2'3'-cGAMP formation is biocatalyzed by cGAMP synthase (cGAS) upon sensing of cytosolic double-stranded DNA (dsDNA) and functions as an endogenous inducer of innate immunity by directly binding to and activating the adaptor protein stimulator of interferon genes (STING). Thereby 2'3'-cGAMP can stimulate interferon-β (INF-β) secretion, a major signaling pathway of host defense, which is independent of toll-like receptor (TLR) activation. Medicinal chemistry of 2'3'-cGAMP and development of corresponding analogs are still in their infancy, and only a handful of structurally related compounds are available to the scientific community. The aim of this chapter is to summarize synthetic approaches to prepare canonical and noncanonical endogenous CDNs including 2'3'-cGAMP. Furthermore, we will describe syntheses of 2'3'-cGAMP analogs bearing modifications, which will facilitate further studies of the emerging biological functions of 2'3'-cGAMP and to identify additional receptor proteins. Finally, we will review latest developments concerning 2'3'-cGAMP analogs with improved hydrolytic stability in cell cultures and in tissues, putatively qualifying for new therapeutic options on the basis of 2'3'-cGAMP signaling.

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Chemistry of Cyclic Dinucleotides and Analogs

Saito–Tarashima

Minakawa

2022

Handbook of Chemical Biology of Nucleic Acids

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New Approach for the Synthesis of c-di-GMP and Its Analogues

Abstract: The synthesis of cyclic bis(3¢-5¢)diguanylic acid (c-di-GMP) by using a new flexible approach is reported. The flexibility of the method is exemplified by the synthesis of base-modified analogues that will find applications in the elucidation of c-di-GMP biological modes of action.

Cited by 7 publications

References 24 publications

Design and Synthesis of Cyclic Dinucleotide Analogues Containing Triazolyl C-Nucleosides

Design and Synthesis of Cyclic Dinucleotide Analogues Containing Triazolyl C-Nucleosides

The Chemistry of the Noncanonical Cyclic Dinucleotide 2′3′-cGAMP and Its Analogs

Chemistry of Cyclic Dinucleotides and Analogs

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