Chapter 31 

 Chemical and Enzymic Synthesis of Polynucleotides 



H. Gobind Khorana* 



British Columbia Research Council, University of British 

 Columbia, Vancouver, Canada 



I. Abbreviated Formulations and Nomenclature of Polynucleotides 105 



1. Abbreviated Formulations 105 



2. Diagrammatic Representations 106 



3. Nomenclature 106 



II. Chemical Synthesis of Polynucleotides 108 



1. Methods for the Synthesis of Internucleotide (Phosphodiester) Bonds. . . 109 



2. Stepwise Synthesis of Deoxyribo-oligonucleotides 113 



3. The Specific Synthesis of Tnterribonucleotide Bonds 117 



4. Polymerization of Mononucleotides 118 



III. Enzymic Synthesis of Ribopolynucleotides 124 



1 . Introduction 124 



2. Ribonucleoside-5'-Diphosphates as Precursors of Ribopolynucleotides. . 124 



3. Ribonucleoside-5'-Triphosphates as Precursors of Ribopolynucleotides 



in Mammalian Systems 132 



IV. Enzymic Synthesis of Deoxyribopolynucleotides 136 



1 . Microorganisms 137 



2. Mammalian Systems 145 



I. Abbreviated Formulations and Nomenclature of Polynucleotides 1 



1. Abbreviated Formulations 



Shorthand formulations for ribo-oligonucleotides were first introduced 

 by Markham and co-workers. 2, 3 These are convenient and useful and have 

 been largely accepted. The letters A, U, G and C represent the nucleosides 

 of, respectively, adenine, uracil, guanine, and cytosine. The letter "p" to 

 the left of the nucleoside initial indicates a 5'-phosphomonoester group, 

 while the same letter to the right, a 3'-phosphate. The 2 '-deoxyribo-oligo- 

 nucleotides may be distinguished from their ribo-counterparts by prefixing 



*Present address: Institute for Enzyme Research, The University of Wisconsin, 

 Madison, Wisconsin. 



1 Polynucleotides derived from the ribose and deoxyribose series have often been 

 named polyribonucleotides and polydeoxyribonucleotides. It seems more appro- 

 priate to use the alternative names ribopolynucleotides and deoxyribopolynucleo- 

 tides. These names are adopted in this article. 



■ R. Markham and J. D. Smith, Biochem. J. 52, 558 (1952). 



3 L. A. Heppel, P. R. Whitfeld, and R. Markham, Biochem. J. 60, 8 (1955). 



105 



