An Improved Strategy for the Chemical Synthesis of 3′,5′‐Cyclic Diguanylic Acid
Abstract
Abstract The physiological functions of c‐di‐GMP and its involvement in many key processes led to its recognition as a major and ubiquitous bacterial second messenger. Aside from being a bacterial signaling molecule, c‐di‐GMP is also an immunostimulatory molecule capable of inducing innate and adaptive immune responses through maturation of immune mammalian cells. Given the broad biological functions of c‐di‐GMP and its potential applications as a nucleic‐acid‐based drug, the chemical synthesis of c‐di‐GMP has drawn considerable interest. An improved phosphoramidite approach to the synthesis of c‐di‐GMP is reported herein. The synthetic approach is based on the use of a 5′‐ O ‐formyl protecting group, which can be rapidly and chemoselectively cleaved from a key dinucleotide phosphoramidite intermediate to enable a cyclocondensation reaction leading to a fully protected c‐di‐GMP product in a yield ∼80%. The native c‐di‐GMP is isolated, after complete deprotection, in an overall yield of 36% based on the commercial ribonucleoside used as starting material. © 2019 by John Wiley & Sons, Inc.
- Authors:
-
- Laboratory of Biological Chemistry, Food and Drug Administration Silver Spring Maryland
- ChemGenes Corporation Wilmington Massachusetts
- Publication Date:
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1506162
- Resource Type:
- Publisher's Accepted Manuscript
- Journal Name:
- Current Protocols in Nucleic Acid Chemistry
- Additional Journal Information:
- Journal Name: Current Protocols in Nucleic Acid Chemistry Journal Volume: 77 Journal Issue: 1; Journal ID: ISSN 1934-9270
- Publisher:
- Wiley Blackwell (John Wiley & Sons)
- Country of Publication:
- Country unknown/Code not available
- Language:
- English
Citation Formats
Grajkowski, Andrzej, Takahashi, Mayumi, Kaczyński, Tomasz, Srivastava, Suresh C., and Beaucage, Serge L. An Improved Strategy for the Chemical Synthesis of 3′,5′‐Cyclic Diguanylic Acid. Country unknown/Code not available: N. p., 2019.
Web. doi:10.1002/cpnc.84.
Grajkowski, Andrzej, Takahashi, Mayumi, Kaczyński, Tomasz, Srivastava, Suresh C., & Beaucage, Serge L. An Improved Strategy for the Chemical Synthesis of 3′,5′‐Cyclic Diguanylic Acid. Country unknown/Code not available. https://doi.org/10.1002/cpnc.84
Grajkowski, Andrzej, Takahashi, Mayumi, Kaczyński, Tomasz, Srivastava, Suresh C., and Beaucage, Serge L. Wed .
"An Improved Strategy for the Chemical Synthesis of 3′,5′‐Cyclic Diguanylic Acid". Country unknown/Code not available. https://doi.org/10.1002/cpnc.84.
@article{osti_1506162,
title = {An Improved Strategy for the Chemical Synthesis of 3′,5′‐Cyclic Diguanylic Acid},
author = {Grajkowski, Andrzej and Takahashi, Mayumi and Kaczyński, Tomasz and Srivastava, Suresh C. and Beaucage, Serge L.},
abstractNote = {Abstract The physiological functions of c‐di‐GMP and its involvement in many key processes led to its recognition as a major and ubiquitous bacterial second messenger. Aside from being a bacterial signaling molecule, c‐di‐GMP is also an immunostimulatory molecule capable of inducing innate and adaptive immune responses through maturation of immune mammalian cells. Given the broad biological functions of c‐di‐GMP and its potential applications as a nucleic‐acid‐based drug, the chemical synthesis of c‐di‐GMP has drawn considerable interest. An improved phosphoramidite approach to the synthesis of c‐di‐GMP is reported herein. The synthetic approach is based on the use of a 5′‐ O ‐formyl protecting group, which can be rapidly and chemoselectively cleaved from a key dinucleotide phosphoramidite intermediate to enable a cyclocondensation reaction leading to a fully protected c‐di‐GMP product in a yield ∼80%. The native c‐di‐GMP is isolated, after complete deprotection, in an overall yield of 36% based on the commercial ribonucleoside used as starting material. © 2019 by John Wiley & Sons, Inc.},
doi = {10.1002/cpnc.84},
journal = {Current Protocols in Nucleic Acid Chemistry},
number = 1,
volume = 77,
place = {Country unknown/Code not available},
year = {Wed Apr 10 00:00:00 EDT 2019},
month = {Wed Apr 10 00:00:00 EDT 2019}
}
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