Polynucleotide complexes synthesis

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 polycondensation method has as yet been elaborated only for polymers with 1,2-trans-glycosidic linkages between the repeating units, but within these limits it seems to be a rather broad chemical method. It is the first purely chemical method for the synthesis of complex polysaccharides, as was demonstrated before for polypeptides and polynucleotides. ... 

Polynucleotide polymerases, or nucleotidyl transferases, are enzymes that catalyze the template-instructed polymerization of deoxyribo- or ribonu-cleoside triphosphates into polymeric nucleic acid - DNA or RNA. Depending on their substrate specificity, polymerases are classed as RNA- or DNA-dependent polymerases which copy their templates into RNA or DNA (all combinations of substrates are possible). Polymerization, or nucleotidyl transfer, involves formation of a phosphodiester bond that results from nucleophilic attack of the 3 -OH of primer-template on the a-phosphate group of the incoming nucleoside triphosphate. Although substantial diversity of sequence and function is observed for natural polymerases, there is evidence that many employ the same mechanism for DNA or RNA synthesis. On the basis of the crystal structures of polymerase replication complexes, a two-metal-ion mechanism of nucleotide addition was proposed [1] during this two divalent metal ions stabilize the structure and charge of the expected pentacovalent transition state (Figure B.16.1). 

Nature has evolved very sophisticated mechanisms for making exact polypeptides and polynucleotides. In contrast, saccharides are made in an apparent random fashion with a diverse set of enzymes competing to produce very diverse products. Although random in appearance, carbohydrates do possess precise structures that are on the surface of complex large molecules and that affect function. These precise carbohydrate structures are targets of isolation and synthesis. 

Michalski and coworkers have shown that sulphuryl chloride fluoride (25) is a convenient reagent for preparing both simple phosphorofluoridates and more complex carbo-hydrate-substituted phosphorofluoridates for use in polynucleotide synthesis. Using phosphorus (III) trimethylsilyl esters (equation 20), products of very high purity are obtained in excellent yields under mild reaction conditions. Alternatively, phosphorus(V) thionophosphate or selenophosphate esters (equation 21) and 25 also give the corresponding phosphorofluoridates in high yields. ... 

Metal ions are known to be essential for many of the bio functions of DNA and RNA, although in some cases these functions are only partially understood. Metal ions are needed for the function of enzymes which act on nucleic acids but DNA synthesis is inhibited by complex formation with metal atoms such as Pt. Metal ions are frequently involved in the interaction of drug molecules with the polynucleotide chain—a subject which has become of major importance (Chapters 12.13 and 11.6). 

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