Chemical synthesis polynucleotides

Nucleic acids are the molecules of the genetic apparatus. They direct protein biosynthesis in the body and are the raw materials of genetic technology (see Genetic engineering). Most often polynucleotides are synthesized microbiologicaHy, or at least enzymatically, but chemical synthesis is possible. 

Some six hundred structures of naturally occurring carbogenic molecules appe on the pages which follow, together with the name of each compound and references to the original literature of successful chemical synthesis. Thus, Part Three of this book is effectively a key to the literature of chemical synthesis as applied to the complex molecules of nature. The survey does not include oligomeric or polymeric structures, such as peptides, proteins, carbohydrates and polynucleotides, which fall outside the scope of this book because they can be assembled by repetitive procedures. 

The chemical synthesis involves a lot more selective manipulation of functional groups, particularly by protection, than is necessary in the biological synthesis. However, this synthesis paved the way to the simple syntheses of nucleotides and polynucleotides carried out routinely nowadays. The usual method is to build short runs of nucleotides and then let the enzymes copy them—a real partnership between biology and chemistry. 

The Letsinger-Caruthers synthesis is unrelated to the biochemical one except in the area of efficiency. Because phosphites are so reactive, they would be totally unsuitable for the genetic tape itself, but because they are so reactive, they are ideally suited as intermediates in the chemical synthesis of polynucleotides. One can accomplish the needed condensation reactions with phosphites under strictly anhydrous conditions with very weakly acidic catalysts, and then stabilize the product by a mild oxidation of the phosphite to the desired phosphate with iodine. 

Polynucleotides possess a great many reactive groups (see Figure 29-1), which must be protected before a conventional chemical synthesis of polynucleotides via the sugar-phosphate polycondensation reaction can be performed. Consequently, an enzymatic synthesis is generally preferred. 

Chemical Synthesis of Oligonucleotides and Polynucleotides of Defined Sequences.—... 

Weber, H. and Khorana, H. G. (1968) Studies on polynucleotides. CIV. Total synthesis of the strac-tural gene for an alanine transfer ribonucleic acid for yeast. Chemical synthesis of an icosadeoxyribo-nucleotide corresponding to the nucleotide sequence 21-40. J. Molec. Biol. 72,219 (and accompanying papers). 

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