Frederik Sanger

Frederik Sanger
Frederik Sanger
Lični podaci
Datum rođenja	(1918-08-13)13. avgust 1918.
Mesto rođenja	Rendkoum, Ujedinjeno Kraljevstvo
Datum smrti	19. novembar 2013.(2013-11-19) (95 god.)
Mesto smrti	Kembridž, Ujedinjeno Kraljevstvo
Obrazovanje	Univerzitet u Kembridžu, St John's College
Naučni rad
Polje	hemija
Nagrade	Nobelova nagrada za hemiju (1958 i 1980)

Frederik Sanger (engl. Frederick Sanger; Rendkoum, 13. avgust 1918 — 19. novembar 2013) bio je britanski biohemičar. Sanger je jedini naučnik koji je dobio dve Nobelove nagrade za hemiju.

Objasnio je konstitucionu strukturu molekula insulina, što mu je uz rad na istraživanju sekvenci proteina donelo Nobelovu nagradu za hemiju 1958. Za istraživanje strukture molekula DNK, nagrađen je još jednom Nobelovom nagradom 1980, ovaj put zajedno sa Polom Bergom i Volterom Gilbertom.

Istraživački rad

Sanger je utvrdio sekvencu aminokiselina u insulinu 1955. Tako je dokazao da proteini imaju određenu, a ne haotičnu strukturu. Istraživanje je započeo kidajući molekul insulina i to pomoću enzima tripsina. Tripsin raskida peptidne veze između aminokiselina (lizina i arginina). Onda je na dobijenu smesu primenio hromatografske metode, tako što bi naneo malu kap smese na jedan kraj filter papira. Onda bi propustio rastvarač kroz filter papir u jednom smeru, a električnu struju u drugom. Zavisno od toga koliko su fragmenti proteina rastvorljivi, odnosno kakve su im električne osobine, oni bi se grupisali u određenoj šari na filter papiru. Sanger je ove šare nazivao „otisci prstiju“. Poput ljudskih otisaka prsta, ove šare su bile posebne za svaki pojedini protein, i svaki put bi se formirale u istom obliku. Zatim je kraće fragmente rekombinovao da bi dedukcijom došao do originalnog molekula insulina.

Godine 1975, razvio je metodu za pronalaženje strukture DNK molekula pod imenom Sangerova metoda (engl. Dideoxy termination). Dve godine kasnije uspešno je dekodirao sekvencu gena fage Φ-X174. To je bio prvi organizam čija je sekvenca DNK dešifrovana. Ceo proces je sproveo ručno. Ovo dostignuće je bilo ključna etapa ka projektu dešifrovanja ljudskog genoma.

Odabrane publikacije

• Neuberger, A.; Sanger, F. (1942), „The nitrogen of the potato”, Biochemical Journal, 36 (7–9): 662—671, PMC 1266851 , PMID 16747571, doi:10.1042/bj0360662 .
• Neuberger, A.; Sanger, F. (1944), „The metabolism of lysine”, Biochemical Journal, 38 (1): 119—125, PMC 1258037 , PMID 16747737, doi:10.1042/bj0380119 .
• Sanger, F. (1945), „The free amino groups of insulin”, Biochemical Journal, 39 (5): 507—515, PMC 1258275 , PMID 16747948, doi:10.1042/bj0390507 .
• Sanger, F. (1947), „Oxidation of insulin by performic acid”, Nature, 160 (4061): 295—296, Bibcode:1947Natur.160..295S, PMID 20344639, S2CID 4127677, doi:10.1038/160295b0 .
• Porter, R.R.; Sanger, F. (1948), „The free amino groups of haemoglobins”, Biochemical Journal, 42 (2): 287—294, PMC 1258669 , PMID 16748281, doi:10.1042/bj0420287 .
• Sanger, F. (1949a), „Fractionation of oxidized insulin”, Biochemical Journal, 44 (1): 126—128, PMC 1274818 , PMID 16748471, doi:10.1042/bj0440126 .
• Sanger, F. (1949b), „The terminal peptides of insulin”, Biochemical Journal, 45 (5): 563—574, PMC 1275055 , PMID 15396627, doi:10.1042/bj0450563 .
• Sanger, F.; Tuppy, H. (1951a), „The amino-acid sequence in the phenylalanyl chain of insulin. 1. The identification of lower peptides from partial hydrolysates”, Biochemical Journal, 49 (4): 463—481, PMC 1197535 , PMID 14886310, doi:10.1042/bj0490463 .
• Sanger, F.; Tuppy, H. (1951b), „The amino-acid sequence in the phenylalanyl chain of insulin. 2. The investigation of peptides from enzymic hydrolysates”, Biochemical Journal, 49 (4): 481—490, PMC 1197536 , PMID 14886311, doi:10.1042/bj0490481 .
• Sanger, F.; Thompson, E.O.P. (1953a), „The amino-acid sequence in the glycyl chain of insulin. 1. The identification of lower peptides from partial hydrolysates”, Biochemical Journal, 53 (3): 353—366, PMC 1198157 , PMID 13032078, doi:10.1042/bj0530353 .
• Sanger, F.; Thompson, E.O.P. (1953b), „The amino-acid sequence in the glycyl chain of insulin. 2. The investigation of peptides from enzymic hydrolysates”, Biochemical Journal, 53 (3): 366—374, PMC 1198158 , PMID 13032079, doi:10.1042/bj0530366 .
• Sanger, F.; Thompson, E.O.P.; Kitai, R. (1955), „The amide groups of insulin”, Biochemical Journal, 59 (3): 509—518, PMC 1216278 , PMID 14363129, doi:10.1042/bj0590509 .
• Ryle, A.P.; Sanger, F.; Smith, L.F.; Kitai, R. (1955), „The disulphide bonds of insulin”, Biochemical Journal, 60 (4): 541—556, PMC 1216151 , PMID 13249947, doi:10.1042/bj0600541 .
• Brown, H.; Sanger, F.; Kitai, R. (1955), „The structure of pig and sheep insulins”, Biochemical Journal, 60 (4): 556—565, PMC 1216152 , PMID 13249948, doi:10.1042/bj0600556 .
• Sanger, F. (1959), „Chemistry of Insulin: determination of the structure of insulin opens the way to greater understanding of life processes”, Science, 129 (3359): 1340—1344, Bibcode:1959Sci...129.1340G, PMID 13658959, doi:10.1126/science.129.3359.1340 .
• Milstein, C.; Sanger, F. (1961), „An amino acid sequence in the active centre of phosphoglucomutase”, Biochemical Journal, 79 (3): 456—469, PMC 1205670 , PMID 13771000, doi:10.1042/bj0790456 .
• Marcker, K.; Sanger, F. (1964), „N-formyl-methionyl-S-RNA”, Journal of Molecular Biology, 8 (6): 835—840, PMID 14187409, doi:10.1016/S0022-2836(64)80164-9 .
• Sanger, F.; Brownlee, G.G.; Barrell, B.G. (1965), „A two-dimensional fractionation procedure for radioactive nucleotides”, Journal of Molecular Biology, 13 (2): 373—398, PMID 5325727, doi:10.1016/S0022-2836(65)80104-8 .
• Brownlee, G.G.; Sanger, F.; Barrell, B.G. (1967), „Nucleotide sequence of 5S-ribosomal RNA from Escherichia coli”, Nature, 215 (5102): 735—736, Bibcode:1967Natur.215..735B, PMID 4862513, S2CID 4270186, doi:10.1038/215735a0 .
• Brownlee, G.G.; Sanger, F. (1967), „Nucleotide sequences from the low molecular weight ribosomal RNA of Escherichia coli”, Journal of Molecular Biology, 23 (3): 337—353, PMID 4291728, doi:10.1016/S0022-2836(67)80109-8 .
• Brownlee, G.G.; Sanger, F.; Barrell, B.G. (1968), „The sequence of 5S ribosomal ribonucleic acid”, Journal of Molecular Biology, 34 (3): 379—412, PMID 4938553, doi:10.1016/0022-2836(68)90168-X .
• Adams, J.M.; Jeppesen, P.G.; Sanger, F.; Barrell, B.G. (1969), „Nucleotide sequence from the coat protein cistron of R17 bacteriophage RNA”, Nature, 223 (5210): 1009—1014, Bibcode:1969Natur.223.1009A, PMID 5811898, S2CID 4152602, doi:10.1038/2231009a0 .
• Barrell, B.G.; Sanger, F. (1969), „The sequence of phenylalanine tRNA from E. coli”, FEBS Letters, 3 (4): 275—278, PMID 11947028, S2CID 34155866, doi:10.1016/0014-5793(69)80157-2  .
• Jeppesen, P.G.; Barrell, B.G.; Sanger, F.; Coulson, A.R. (1972), „Nucleotide sequences of two fragments from the coat-protein cistron of bacteriophage R17 ribonucleic acid”, Biochemical Journal, 128 (5): 993—1006, PMC 1173988 , PMID 4566195, doi:10.1042/bj1280993h .
• Sanger, F.; Donelson, J.E.; Coulson, A.R.; Kössel, H.; Fischer, D. (1973), „Use of DNA Polymerase I Primed by a Synthetic Oligonucleotide to Determine a Nucleotide Sequence in Phage f1 DNA”, Proceedings of the National Academy of Sciences USA, 70 (4): 1209—1213, Bibcode:1973PNAS...70.1209S, PMC 433459 , PMID 4577794, doi:10.1073/pnas.70.4.1209 .
• Sanger, F.; Coulson, A.R. (1975), „A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase”, Journal of Molecular Biology, 94 (3): 441—448, PMID 1100841, doi:10.1016/0022-2836(75)90213-2 .
• Sanger, F.; Nicklen, S.; Coulson, A.R. (1977), „DNA sequencing with chain-terminating inhibitors”, Proceedings of the National Academy of Sciences USA, 74 (12): 5463—5467, Bibcode:1977PNAS...74.5463S, PMC 431765 , PMID 271968, doi:10.1073/pnas.74.12.5463 . According to the Institute for Scientific Information (ISI) database, by October 2010 this paper had been cited over 64,000 times.
• Sanger, F.; Air, G.M.; Barrell, B.G.; Brown, N.L.; Coulson, A.R.; Fiddes, C.A.; Hutchinson, C.A.; Slocombe, P.M.; Smith, M. (1977), „Nucleotide sequence of bacteriophage φX174 DNA”, Nature, 265 (5596): 687—695, Bibcode:1977Natur.265..687S, PMID 870828, S2CID 4206886, doi:10.1038/265687a0 .
• Sanger, F.; Coulson, A.R. (1978), „The use of thin acrylamide gels for DNA sequencing”, FEBS Letters, 87 (1): 107—110, PMID 631324, S2CID 1620755, doi:10.1016/0014-5793(78)80145-8  .
• Sanger, F.; Coulson, A.R.; Barrell, B.G.; Smith, A.J.; Roe, B.A. (1980), „Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing”, Journal of Molecular Biology, 143 (2): 161—178, PMID 6260957, doi:10.1016/0022-2836(80)90196-5 .
• Anderson, S.; Bankier, A.T.; Barrell, B.G.; De Bruijn, M.H.; Coulson, A.R.; Drouin, J.; Eperon, I.C.; Nierlich, D.P.; Roe, B.A.; Sanger, F.; Schreier, P.H.; Smith, A.J.; Staden, R.; Young, I.G. (1981), „Sequence and organization of the human mitochondrial genome”, Nature, 290 (5806): 457—465, Bibcode:1981Natur.290..457A, PMID 7219534, S2CID 4355527, doi:10.1038/290457a0 .
• Anderson, S.; De Bruijn, M.H.; Coulson, A.R.; Eperon, I.C.; Sanger, F.; Young, I.G. (1982), „Complete sequence of bovine mitochondrial DNA. Conserved features of the mammalian mitochondrial genome”, Journal of Molecular Biology, 156 (4): 683—717, PMID 7120390, doi:10.1016/0022-2836(82)90137-1 .
• Sanger, F.; Coulson, A.R.; Hong, G.F.; Hill, D.F.; Petersen, G.B. (1982), „Nucleotide sequence of bacteriophage λ DNA”, Journal of Molecular Biology, 162 (4): 729—773, PMID 6221115, doi:10.1016/0022-2836(82)90546-0 .
• Sanger, F. (1988), „Sequences, sequences, and sequences”, Annual Review of Biochemistry, 57: 1—28, PMID 2460023, doi:10.1146/annurev.bi.57.070188.000245  .

Literatura

• Brownlee, George G. (2014). Fred Sanger, double Nobel laureate: a biography. Cambridge, UK: Cambridge University Press. ISBN 978-1-107-08334-9.  Chapters 4-6 contain the 1992 interview that the author conducted with Sanger.
• Finch, John (2008), A Nobel Fellow on every floor: a history of the Medical Research Council Laboratory of Molecular Biology, Cambridge: Medical Research Council, ISBN 978-1-84046-940-0 .
• García-Sancho, Miguel (2010). „A new insight into Sanger's development of sequencing: from proteins to DNA, 1943–1977” (PDF). Journal of the History of Biology. 43 (2): 265—323. PMID 20665230. S2CID 1134280. doi:10.1007/s10739-009-9184-1. hdl:20.500.11820/e4febe48-772a-4f47-a1c5-a5ca89505367 . 
• Sanger, F.; Dowding, M. (1996), Selected Papers of Frederick Sanger: with commentaries, Singapore: World Scientific, ISBN 978-981-02-2430-1 .
• The Sanger Institute
• About the 1958 Nobel Prize
• About the 1980 Nobel Prize
• Fred Sanger 2001 Video Documentary by The Vega Science Trust
• National Portrait Gallery Arhivirano na sajtu Wayback Machine (25. oktobar 2008)
• Frederick Sanger interviewed by Alan Macfarlane, 24 August 2007 (video), also available on 0JsrvWYS7zY na sajtu YouTube. Duration 57 minutes.
• Interviews with Nobel Prize–winning scientists: Dr Frederick Sanger, British Broadcasting Corporation, c. 1985 . Interviewed by Lewis Wolpert. Duration 1 hour.
• Frederick Sanger archive collection - Wellcome Library finding aid for the digitised collection.

Spoljašnje veze

• Autobiografija