Guanine discovery

The discovery of PLCs reveals a fourth mechanism whereby the enzyme can be activated (Fig. 20-5). PLCs possesses two Ras-binding (RA) domains in its carboxyl terminal region, and occupancy of these by Ras-GTP results in activation of the enzyme. In addition, the enzyme possesses a CDC-25 domain at its N-terminus, which serves as a guanine nucleotide exchange factor (GEF) for small GTP-binding proteins such as Ras or RaplA. Thus PLCe can not only activate the GDP-bound forms of these small GTP-binding proteins but can also be... 

Guanine is a crystalline amorphous substance that is found in guano, fish scales, and the liver of certain mammals. Guanine is responsible for the silvery iridescence of certain fish scales. Before its discovery, guanine was scraped from fish scales and used to coat beads to produce imitation pearls. Thus it was called pearl essence or pearly white in the 1700s. Guanine obtained from fish scales is used in cosmetics, especially for eye cosmetics and nail polishes. 

Same of the common names of these bases reflect the circumstances of their discovery. Guanine, for example, was first isolated from guano (bird manure), and thymine was first isolated from thymus tissue. 

Early work on DNA polymerase I led to the definition of two central requirements for DNA polymerization. First, all DNA polymerases require a template. The polymerization reaction is guided by a template DNA strand according to the base-pairing rules predicted by Watson and Crick where a guanine is present in the template, a cytosine deoxynucleotide is added to the new strand, and so on. This was a particularly important discovery, not only because it provided a chemical basis for accurate semiconservative DNA replication but also because it represented the first example of the use of a template to guide a biosynthetic reaction. 

A search for antimetabolites, i.e. analogues of essential metabolites that might displace the latter in vital processes, was proposed as a rational approach to the discovery of antibacterial agents, but it has had little success other than the achievements in the folic acid field (Section 1.06.6). Substances that resemble the components of nucleic acids have, however, had considerable success in the chemotherapy of cancer and of some virus diseases and in the suppression of the immune response. They may act by becoming incorporated in false nucleic acids or by blocking the synthesis of nucleic acids, nucleotides, nucleosides or of the pyrimidine and purine bases cytosine (88), thymine (89 R = Me), adenine (90) and guanine (91 X = CH). The simplest antimetabolites are analogues of these bases. 

Erwin Chargaff s discovery that DNA contains equimolar amounts of guanine and cytosine and also equimolar amounts of adenine and thymine has come to be known as Chargaff s rule ... 

In 1933, Klein discovered that sodium arsenate inhibits the action of the nucleotidase" of intestinal mucosa. Consequently, Klein and Thannhauser were enabled to hydrolyze thymus nucleic acid by means of intestinal desoxyribonucleinase without subsequent dephosphorylation of the liberated nucleotides. Making use, also, of Klein s discovery of the deaminase-inhibiting activity of silver ions, they were successful in isolating the adenine nucleotide. Hence the phosphodesoxyribosyl nucleotides of adenine, guanine, thymine, and cytosine were isolated and characterized. 

Cisplatin (cis-dichlorodiammineplatinum cisDDP) belongs to one of the most frequently explored platinum compounds since Rosenberg s discovery of its anticancer activities.1 It was found that cisplatin makes a bridge connection between two (usually) adjacent guanine bases in DNA predominately forming 1,2-intrastrand GpG complexes (about 65% of the occurrences). Some other intrastrand coordinations occur less frequently, namely with the l,2-d(ApG) and the l,3-d(GpXpG) base sequences. However, coordination to the l,2-d(ApA) or the l,2-d(GpA) fragment was observed only very rarely. 

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