Sanger (Sanger), Frederic

genus. August 13, 1918
English biochemist Frederick Sanger (Sanger) was born in Rendkombe (Gloucestershire), a wealthy Quaker family. His mother, nee Cecily Krusdom, was the daughter of a prosperous textile magnate. His father (incidentally, in his honor and was named AS) was a doctor. From 1932 to 1936. future scientist trained in Brayanstonskoy school in Blandford (county of Dorsetshire), and in 1936. enrolled in the College of St.. John Cambridge. Initially C. planned to go to his father's footsteps and take up medicine, but he became interested in biochemistry. 'It seemed to me - he wrote many years later - that this was the way to real understanding of living matter and to develop a more scientific basis for solving many problems facing medicine'.
In 1939, Mr.. University of Cambridge C. received a bachelor of science. In September the same year, the outbreak of World War II, but the S., as a Quaker, was released from military service and left in Cambridge graduate. Received in 1943. doctorate, he joined the research team, led by E.CH. Chibnallom, who just before it was replaced by Frederick Goulenda Hopkins University as professor of biochemistry at Cambridge University. While Chibnall studied the chemistry of proteins.
In 1902, Mr.. Emil Fischer suggested that the proteins are composed of amino acids linked by peptide bonds. By the early 40-ies. Fisher's hypothesis has been widely, although not universally recognized. When more than two amino acids linked together, they form a polypeptide chain. Because the amino acid can form no more than two peptide bonds, Fisher predicted that the proteins should be composed of linear chains of amino acids with a free carboxyl group (consisting of carbon, oxygen and hydrogen) - on the other. Chibnall suggested C. establish the final grouping of the peptide chain by chemical means. If it was done, it would be found that the proteins actually consist of linear chains of amino acids. In addition, it would indicate, and the fact is if one protein is more than one type of peptide chain.
In 1945, Mr.. S. reported that under mild alkaline conditions specific reagent (dinitrophenol) can be attached to the nitrogen atom through the amino acids connection stronger than the peptide. Consequently, the protein can be split into its component amino acids with the destruction of peptide bonds and amino acids can be identified by chromatography. Chromatography, just before this improved Archer Martin and Richard Singh, allows sharing of material into components, based on the characteristic speed at which they are absorbed by a special filter.
. Much of the research conducted in the laboratory Chibnalla, was associated with insulin, one of the few proteins that are available at the time in pure form and in large quantities
. Initial research with. insulin showed that it contains two different N-terminal amino. Consequently, each insulin molecule consists of two types of polypeptide chains. Amino acid cysteine contains a sulfur molecule, two molecules of cysteine can be connected with the formation of cystine, which has a disulfide bridge or between two polypeptide chains, or between different parts of one chain. In 1949, Mr.. S. reported that he had opened the way to the destruction of the disulfide bridges and, consequently, the method of separation of the two chains.
With. and came from Vienna scientist Hans Tuppi developed a plan to establish a sequence of alternating amino acids in each polypeptide chain of insulin. After breaking the chain of subsections, these two scientists had hoped to establish the sequence of amino acids in each subsection and, on the basis of this information, the sequence of their alternation in the entire polypeptide chain. Despite the fact that C. originally used acid to break the polypeptide chain, he soon discovered that the enzymes are much more accurate. Thus, C. and compared Tuppi chain fragments resulting from the application of different enzymes, to understand the sequence of alternation of amino acids in the chain. Set the sequence of alternation for the longer of the two insulin chains was surprisingly easy, and this work was almost finished by the time Tuppi in 1950, Mr.. left Cambridge. However, the shorter chain insulin is not so easily yield to chemical analysis, and therefore the sequence of alteration of the amino acids it was fully established only in 1953. S. continued work to establish the location of disulfide bridges between two chains, and in 1955. presented a complete structure of the insulin molecule. This was the first protein molecule, as detailed study.
Using. had important implications for the biochemistry and the emerging science - molecular biology. The results of its studies demonstrated conclusively that the proteins are composed of amino acids linked in a chain of peptide bonds. At the beginning of XX century. many chemists believed that proteins are a mixture of related compounds. S., however, found that the protein - is a special chemical substance with a unique structure, and that every place in the chain employs a specific amino acid. He also proved that the enzymes can break the peptide chain in a pre-defined field. Application of this method has helped biochemists to determine the structure of many other proteins.
In 1958, Mr.. S. was awarded the Nobel Prize in Chemistry 'for the establishment of structures of proteins, especially insulin'. In his Nobel lecture with. emphasized the practical importance of his work. 'Establishing the structure of insulin, of course, opens the way to the study of other proteins, - he said. - It is also hoped that the study of proteins can help identify changes that occur in the body during illness, and that our efforts can bring great practical benefit to mankind '.
Even before receiving the Nobel Prize with. began studying the genetics. This was partly under the influence of friendship with the scientist Francis Crick. For C. one of the most striking facts about the sequence of alternation of individual groups in insulin, was the apparent lack of any kind was the principle of the unique location of amino acids. But from this seemingly random order depended on the important physiological activity. S. not understand how a protein can be connected in that order, but it was obvious that this order should be some sources. In the mid 50-ies. Crick (who along with James D. Watson first described the structure of the genetic material deoxyribonucleic acid or DNA) explained made with. open it by using the 'sequence hypothesis', which was that the information that defines the sequence of amino acids in the protein genes are. Later it was found that the genes themselves are a sequence of links, some of which correspond to a specific amino acid.
Nucleic acids - DNA and ribonucleic acid (RNA) - a chain of nucleotides linked. Nucleotide consists of a sugar molecule with a phosphate residue and attached to them one of the four 'core' of molecules. Nucleotides are bound together by phosphate groups and form a polypeptide chain. In the structure of DNA molecules of two parallel chains are spiral staircase configuration. A pair of bases forms a rung of the ladder, combining the special bonds between the chains: adenine (A) with guanine (G), pitozin (C) with thymine (T). Code for amino acids is determined by the sequence of three bases. The building of protein starts with the fact that the corresponding section of the DNA molecule, which includes complete instructions for the collection of compounds, 'unbuttoned lightning' for communication, connecting the bases with each other. Free nucleotides (as horrible floating in the cell) are tied along the open for the sequence of the DNA molecule, forming a mirrored circuit, called messenger RNA (mRNA). The finished chain mRNA leaves the DNA (which then again 'closes the zipper') and moves to the cellular structures, which are called birosomami, where he will meet the protein. Lots more short chain formed mRNA and then move to the side in order to absorb the corresponding free nucleotides, which they then bring back the mRNA for inclusion in the protein structure. These short chains are called transport RNA (tRNA). By that time, when C. began to study nucleic acids on these processes, little was known, but the nukleotidovyh sequences did not know anything at all.
. Sequences of DNA and RNA are very difficult to analyze than protein sequences, because they are longer than
. A typical protein chain can contain up to fifty amino acids, and a typical mRNA contains hundreds of nucleotides. Even a tiny virus DNA consists of thousands of nucleotides. Nevertheless, nucleic acid sequences are easier to decode the, . than protein sequences, . because of their fundamental difference: while each seat in the protein chain can be occupied by any of 20 different amino acids, . There is only 4 'candidate' for each place in the sequence of DNA - nucleotides, . referred to as' A, . T, . C and D (under the name of their bases).,
. In 1958, Mr.
. Robert Y. Halls attempted to establish the sequence of the tRNA chain. Despite the fact that the length of these short chains of less than 100 nucleotides, this work because of the difficulty of establishing the sequence was delayed until 1965. In C. deeply impressed by the work of Holly, but he sought a more efficient method of sequencing that is available to apply to the mRNA chains whose length often reaches several hundreds of nucleotides. In the early 60-ies. He and his colleagues have developed a technology. Applying the enzymes, they break the chains of mRNA into smaller chains, and traced the sequence of each of them separately. Then, based on conclusions about the relationship between the fragments was determined by the sequence in the entire chain.
This approach, however, demanded the mass of time and patience, and C. decided to develop an analytical method for establishing the sequence in the DNA. He did this in 1973. His proposed procedure is that the double chain of DNA molecule was divided into single-chain (called strands), and then the resulting material was grouped into four samples. Each sample begin to restore the original sequence of double chains, based on the template single-chain. But the researchers stopped the recovery process at different nucleotides for each sample either by limiting the concentration of a free nucleotide, . or by placing a specific nucleotide in the chain with such a chemical, . which prevents further synthesis,
. As a result, the reconstructed chain are samples of different lengths, but each ends with the same nucleotide. Then these four samples simultaneously passed through the filter material, called hyperfine acrylamide gel, which separates these chains according to their length, because shorter chains pass through the gel faster. And then the nucleotide sequence of the original strands of DNA can be read directly from the gel by comparing the traces left by the samples.
While P. m his colleagues have worked on this method (named didekoksidnym method type used in this limiting chemical), . American scientists Walter Gilbert and Allan Macks developed another procedure for determining the nucleotide sequences,
. In accordance with their method of fragments of DNA chains of different lengths are obtained by breaking the chain on the specific grounds. This approach resembles the method that used with. to establish the sequences in the protein chains and chains of RNA. As technology S., and Gilbert technology became an essential tool of genetic engineering, although the method C. somewhat more effective when working with very long sequences. In 1978. S. and his colleagues have demonstrated the effectiveness didezoksidnogo method, setting the sequence of 5375 bases in the DNA chain of bacterial virus. This was the first time such a detailed decoding of the DNA chain.
In 1980. S. and Gilbert was awarded half the Nobel Prize in Chemistry 'for his contribution in establishing the basic sequences in nucleic acids'. The other half of the prize was awarded to Paul Berg. These three scientists, said in his opening speech on behalf of the Royal Swedish Academy of Sciences BG. Maelstrom, 'made possible the penetration of even greater depth to our understanding of the relationship between chemical structure and biochemical function of the genetic material'.
In 1983. S. retired from his position at the Medical Research Council. A modest, retiring man, he lives in Cambridge with his wife, Margaret Joan Howe. Marriage to her was registered in 1940. In the couple's two sons and a daughter. S. enjoys sailing and working in the garden.
With. won numerous awards. Among them: Corday-Morgan Medal and Prize, . awarded to him by the British Society of Chemistry (1951), . Prize Fund Alfred Alfred Benzonsa Benzonsa (1966), . Royal Medal of the Royal Society of London (1969), . Annual Award Gardner Fund (1971 and 1979), . Hanbury Memorial Medal of the Pharmaceutical Society of Great Britain (1976), . Copley Medal of Royal Society of London (1977) and Albert L Asker prize for basic medical research (1979),
. S. - Honorary Member of the American Society of Biochemistry and the American National Academy of Sciences, holds honorary degrees from universities of Leicester and Strasbourg, as well as Cambridge and Oxford.