Chemical synthesis of nucleic acids

Merrifield s solid phase peptide synthesis presented a new approach to the chemical synthesis ofbiological macromolecules and the solid phase approach was quickly adapted to other fields. Solid phase oligonucleotide synthesis (SPONS) is another vital development in chemical 

The entire oligo- or polydeoxynucleotide is then detached from the solid support and de-protected to complete the synthesis. After synthesis of the oligo- or polydeoxynucleotide 

Starting with backbone modifications, we will consider first phosphorothioate links that result from the exchange of one non-bridging oxygen atom for a sulphur atom in a given 

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Rational chemical synthesis of nucleic acids would soon become the domain of Har Gobind Khorana (1922- ). Khorana was born to an Indian Hindu family in a tiny village in Punjab (now part of Pakistan). His parents persevered in obtaining a first-rate education for him, and Khorana obtained his Ph.D. in England. Following research appointments with two future Nobel laureates, Vladimir Prelog in Zurich and Alexander R. Todd in Cambridge, Khorana came to the University of British Columbia in 1952. He joined the faculty of the University of Wisconsin in 1960, and moved to MFF in 1970. 

FIGURE 9 An outline of the chemical synthesis of nucleic acids. 

The origin of life probably occurred in three phases (fig. 1.23) (1) The earliest phase was a period of chemical evolution during which the compounds needed for the nu-cleation of life must have been formed. These compounds include the most important class of biological macromolecules, the nucleic acids. In this phase of evolution, the synthesis of nucleic acids was noninstructed. (2) As soon as some nucleic acids were present, physical forces between them must have led to an instructed synthesis, in which the already formed molecules served as templates for the synthesis of new polymers. It seems likely that feedback loops selected out certain nucleic acids for preferential synthesis. At some point during this period of instructed synthesis more nucleic acids and possibly protein macromolecules were formed. The products of this phase of mo-... 

Sulfonamides were the first group of chemotherapeutic agents used for the prevention or treatment of bacterial infections in humans. Sulfonamides (e.g., sulfisoxazole) act by inhibiting bacterial synthesis of folic acid, a chemical required for synthesis of nucleic acid and protein. These drugs competitively inhibit the first step in the synthesis of folic acid—the conversion of para-aminobenzoic acid into dihydrofolic acid. Because humans absorb preformed folic acid from food, sulfonamide inhibition has only a minimal effect on hiunan cells. 

Completely molecularly homogeneous macromolecules, on the other hand, are produced by the structure-conixoWtA synthesis of nucleic acids (Chapter 29) and enzymes (Chapter 30). The molar mass and the chemical structure of the macromolecule produced are determined in this case by a specific morphological arrangement (matrix or template). In the first step, the monomer M is bound to the unit T of the macromolecular matrix, and in the second step, monomeric units joined together as a macromolecule are released from the template. The process is shown schematically as... 

Techniques for both the chemical and enzymatic synthesis of nucleic acids have been extensively developed over recent decades. Of particular importance is the synthesis of short-chain oligonucleotides for purposes of genetic engineering (Chapter 11.6). 

The development of automated soUd phase synthesis of nucleic acids and chemical strategies to incorporate fluorophores at any position along their length, together with the wide array of molecular biological techniques available for their modification has resulted in a system highly amenable to single molecule fluorescent studies. By contrast, proteins, to which we now turn our attention, are rarely synthesized in vitro and thus a different approach needs to be taken. 

In 1968, M. W. Nirenberg, H. G. Khorana, and R. W. Holley were awarded the Nobel Prize in Physiology or Medicine for their work on the genetic code. Working independently, Khorana had mastered the synthesis of nucleic acids, and Holley had discovered the exact chemical structure of tRNA. 

Over the last 30 years or so, the chemical synthesis of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) has constituted one of the most challenging problems in the field of the synthetic organic chemistry of natural products. In more recent times, attention has been focused not on natural nucleic acid fragments, but on the preparation of nucleic acids bearing modified internucleotidic linkages or modified bases in an effort to enhance stability to nucleases and increase cellular uptake. 

Structure and Function of Nucleic Acids Nucleic Acid Syntheses DNA Replication and Its Regulation Maintenance of Genome Integrity DNA Manipulations and Their Applications Transcriptional Prooesses Chemical Synthesis of Nuolelo Acids (Oligonucleotides)... 

Dacarbazine is activated by photodecomposition (chemical breakdown caused by radiant energy) and by enzymatic N-demethylation. Formation of a methyl carbonium ion results in methylation of DNA and RNA and inhibition of nucleic acid and protein synthesis. Cells in all phases of the cell cycle are susceptible to dacarbazine. The drug is not appreciably protein bound, and it does not enter the central nervous system. 

Deoxyribonucleic acid (DNA) belongs to a group of chemicals called the nucleic acids (Figure 15.26) They are also biopolymers. DNA controls the prote synthesis within your cells. When you eat a food containing proteins, such as meat or cheese, your digestive enzymes break down the proteins present into individual amino acids. The DNA in your cells controls the order in which the amino acids are repolymerised to make the proteins you need ... 

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