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Sanger, Frederick

sequence chains dna acids

(1918– ) British biochemist: pioneer of chemical studies on the structure of proteins and nucleic acids; the only double Nobel laureate in chemistry.

Sanger, a physician’s son, graduated in Cambridge in 1939 and researched there through his career, on the staff of the Medical Research Council laboratories from 1951. In the early 1940s he devised a method using 2,4-dinitrofluorobenzene (Sanger’s reagent) to label the amino acid at the ‘free amino’ end of a protein chain. By combining this method with the acid or enzymic break-up of the longer protein chains to give shorter, identifiable fragments, Sanger was able to deduce the sequence of amino acids in the chains of the protein hormone insulin; by the early 1950s he had worked out the sequence of the 51 amino acids in its two-chain molecule and found the small differences in the sequence in insulins from pig, sheep, horse and whale.

After he was awarded a Nobel Prize for this, in 1958, he moved on to the bigger problem of the structure of nucleic acids. These biological macromolecules have double helical chains of nucleotides whose base sequence determines the information carried by the genes. He worked first on RNA, whose chains are of modest length, and then moved to DNA, which has very long chains with up to 108 units in a chain. Sanger used a highly ingenious combination of radioactive labelling, gel electrophoresis and selective enzymes which can split or grow DNA chains at specific points.

By 1977 he and his group were able to deduce the full sequence of bases in the DNA of the virus Phi X 174, with over 5400 bases. Mitochondrial DNA, with 17000 bases, soon followed. Such methods, by 1984, led to the full base sequence in Epstein–Barr virus (EBV), whose genome (the complete set of genes of an organism) is over 150 000 bases long. For his nucleic acid work Sanger shared the 1980 Nobel Prize and became the first to win two Nobel Prizes for chemistry. His work has given new, surprising and detailed knowledge of both proteins and genes and has stimulated others in this field.

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