Proteins directed biological synthesis

In contrast to the biopharmaceuticals discussed thus far (recombinant proteins and gene therapy products), antisense oligonucleotides are manufactured by direct chemical synthesis. Organic synthetic pathways have been developed, optimized and commercialized for some time, as oligonucleotides are widely used reagents in molecular biology. They are required as primers, probes and for the purposes of site-directed mutagenesis. 

Figure 1 The central dogma of molecular biology. The central dogma describes the flow of information between the principle biopolymers of the cell. The primary exchange is shown horizontally, left to right, namely, DNA directs the synthesis of RNA, which in turn directs the synthesis of protein. Alternate observed exchanges are depicted off the horizontal with less prominent lines. The letters "P" and "R" indicate that protein or RNA, respectively, are required for particular exchanges.

S-Adenosyl-L-methionine is the important methyl donor in biological transmethylation to form S-adenosyl-L-homocysteine, which is hydrolyzed to adenosine and homocysteine by S-adenosyl-L-homocysteine hydrolase (E.C. 3.3.1.1) in vivo. However, equilibrium of the S-adenosyl-L-homocysteine hydrolase reaction favors the direction toward synthesis of S-adenosyl-L-homocysteine. Shimizu et al. developed a simple and efficient method for the high yield preparation of S-adenosyl-L-homocysteine with S-adenosyl-L-homocysteine hydrolase of Alcaligenes faecalis, in which the cellular content of S-adenosyl-L-homocysteine hydrolase was about 2.5% of the total soluble protein. S-Adenosyl-r-homocysteine was produced at a concentration of about 80 g I. 1 with a yield of nearly 100% 661. However, when racemic... 

DNA and RNA molecnles direct the synthesis of proteins in the ceU, a subject that is beyond the scope of this book. Introductory texts in biochemistry and molecular biology explain this process. 

Discovery of the structure of DNA in 1953 and subsequent elucidation of how DNA directs synthesis of RNA, which then directs assembly of proteins—the so-called central dogma—were monumental achievements marking the early days of molecular biology. However, the simplified representation of the central dogma as DNA—>RNA— protein does not reflect the role of proteins in the synthesis of nucleic acids. Moreover, as discussed in later chapters, proteins are largely responsible for regulating gene expression, the entire process whereby the information encoded in DNA is decoded into the proteins that characterize various cell types. 

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