Nucleobase Protection of Deoxyribo‐ and Ribonucleosides

Geeta Meher1, Nabin K. Meher2, Radhakrishnan P. Iyer1

1 Spring Bank Pharmaceuticals, Inc., Milford, Massachusetts, 2 PharmAgra Labs, Inc., Brevard, North Carolina
Publication Name:  Current Protocols in Nucleic Acid Chemistry
Unit Number:  Unit 2.1
DOI:  10.1002/cpnc.32
Online Posting Date:  June, 2017
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Abstract

Oligonucleotides carrying a variety of chemical modifications including conjugates are finding increasing applications in therapeutics, diagnostics, functional genomics, proteomics, and as research tools in chemical and molecular biology. The successful synthesis of oligonucleotides primarily depends on the use of appropriately protected nucleoside building blocks including the exocyclic amino groups of the nucleobases, the hydroxyl groups at the 2′‐, 3′‐, and 5′‐positions of the sugar moieties, and the internucleotide phospho‐linkage. This unit is a thoroughly revised update of the previously published version and describes the recent development of various protecting groups that facilitate reliable oligonucleotide synthesis. In addition, various protecting groups for the imide/lactam function of thymine/uracil and guanine, respectively, are described to prevent irreversible nucleobase modifications that may occur in the presence of reagents used in oligonucleotide synthesis. © 2017 by John Wiley & Sons, Inc.

Keywords: carbamates; cyanoethylation; depurination; nucleobases; N‐acylation; photolytic cleavage; silyl protection

     
 
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Table of Contents

  • Salient Features of Oligonucleotide Synthesis
  • General Aspects of Nucleobase Protection
  • Nucleoside Tautomerism and PKA Values
  • Reactivity of Nucleosides
  • Protection of Imide and Lactam Functions
  • Protection of Exocyclic Amino Groups
  • The Problem of Cyano‐Ethylation
  • Protection of Purine Nucleobases: The Problem of Depurination
  • Other Developments in Nucleobase Protection
  • Conclusion
  • Acknowledgments
  • Literature Cited
  • Figures
  • Tables
     
 
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Materials

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Literature Cited

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