弗雷德里克·桑格：修订间差异

弗雷德里克·桑格
弗雷德里克·桑格
出生	1918年8月13日（105歲）; 英格蘭，格洛斯特郡
国籍	英國
母校	劍橋大學聖約翰學院
奖项	诺贝尔化学奖 (1958年); 诺贝尔化学奖 (1980年)
	科学生涯
研究领域	生物化學

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2012年8月22日 (三) 15:16的版本

弗雷德里克·桑格，OM，CH，CBE，FRS（Frederick Sanger，1918年8月13日—）是一位英國生物化學家，曾經在1958年及1980年兩度獲得諾貝爾化學獎，是第四位兩度獲得諾貝爾獎，以及唯一獲得兩次化學獎的人。

早年

桑格於1918年 8月13日出生於英國格洛斯特郡，父親是一位醫生。從布萊恩斯滕高中（Bryanston School）畢業後，桑格進入了劍橋大學聖約翰學院，並於1939年完成自然科學文學士學位。他原本打算研究醫學，但後來轉而對生物化學感興趣，而劍橋在當時也正好有許多早期的生物化學先驅。桑格在1943年獲得哲學博士學位。他在1940年時與玛格丽特·瓊·豪（Margaret Joan Howe）結婚，他們育有兩個兒子和一個女兒。

蛋白質與DNA序列研究

桑格在1955年將胰島素的胺基酸序列完整地定序出來，同時證明蛋白質具有明確構造。他利用自己新發現的桑格試劑^[1]，也就是2,4-二硝基氟苯（2,4-dinitrofluorobenzene）將胰島素降解成小片段，並與專門水解蛋白質的胰蛋白酶混合在一起。再將一部分混合物的樣本置放於濾紙的一面，並利用一種色層分析方法來做進一步的實驗，首先他將一種溶劑從單一方向通過濾紙，同時又讓電流以相反向通過。

由於不同的蛋白質片段有不同的溶解度與電荷，因此在电泳后，這些片段最後會各自停留在不同的位置，產生特定的圖案。桑格將此圖案稱為「指紋」；不同的蛋白質擁有不同的圖案，成為可供辨識且可重現的特徵。之後桑格又將小片段從新組合成胺基酸長鏈，進而推導出完整的胰島素結構。因此得出結論，認為胰島素具有特定的胺基酸序列。這項研究使他單獨獲得了1958年的諾貝爾化學獎。

1975年時，桑格發展出一種稱為鏈終止法（chain termination method）的技術來測定DNA序列，這種方法也稱做「雙去氧終止法」（Dideoxy termination method）或是「桑格法」^[2]。兩年之後，他利用此技術成功定序出Φ-X174噬菌體（Phage Φ-X174）的基因組序列。這也是首次完整的基因組定序工作。他所發明的技術比起當時其他方法使用了較不具毒性的材料。主要是先進行PCR，利用DNA引子和DNA聚合酶使DNA鏈得以展開複製，再利用雙去氧核苷酸（dideoxynucleotides）來終止DNA鏈的合成。實驗會使不同序列的DNA帶有不同長度，使其得以經由電泳來做分析。

這項研究後來成為人類基因組計畫等研究得以展開的關鍵之一，並使桑格於1980年再度獲得諾貝爾化學獎，與桑格合作研究的沃特·吉爾伯特，以及另一團隊的保羅·伯格（Paul Berg）也一同獲獎。第二座諾貝爾獎使他成為繼瑪莉·居禮、萊納斯·鮑林，以及約翰·巴丁之後的第四位兩度獲獎者。到了1979年，桑格又與吉爾伯特和伯格一同獲得哥倫比亞大學的路易莎·格羅斯·霍維茨獎（Louisa Gross Horwitz Prize）。

近年影響

桑格於1982年退休，英國的維康信託基金會（Wellcome Trust）和醫學研究理事會（Medical Research Council），於1993年成立了桑格中心（Sanger Centre）^[3]，這座研究機構現在稱為桑格研究院（Sanger Institute），地點位於英國劍橋，是世界上進行基因組研究的主要機構之一。2007年，維康信託提供英國生物化學學會（British Biochemical Society）一項補助，使其為桑格從1989年以後的實驗研究紀錄進行建檔及保存。

其他名譽及頭銜

1954年成為皇家學會院士（FRS）。
1963年獲得英帝國司令勳章（CBE）。
1981年獲得名譽勳位（CH）。
1986年獲得功績勳章（OM）。

參考來源

^ 廖重葳鄭景徽蔡昌樺。Frederick Sanger (1918-)，微生物的世界，東吳大學。
^ Sanger F, Nicklen S, Coulson AR., DNA sequencing with chain-terminating inhibitors, Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7
^ Introduction to the Sanger Institute - Sanger Institute

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Sanger, F.; Tuppy, H., The amino-acid sequence in the phenylalanyl chain of insulin. 1. The identification of lower peptides from partial hydrolysates, Biochemical Journal, 1951a, 49 (4): 463–481, PMC 1197535 , PMID 14886310 .
Sanger, F.; Tuppy, H., The amino-acid sequence in the phenylalanyl chain of insulin. 2. The investigation of peptides from enzymic hydrolysates, Biochemical Journal, 1951b, 49 (4): 481–490, PMC 1197536 , PMID 14886311 .
Sanger, F.; Thompson, E.O.P., The amino-acid sequence in the glycyl chain of insulin. 1. The identification of lower peptides from partial hydrolysates, Biochemical Journal, 1953a, 53 (3): 353–366, PMC 1198157 , PMID 13032078 .
Sanger, F.; Thompson, E.O.P., The amino-acid sequence in the glycyl chain of insulin. 2. The investigation of peptides from enzymic hydrolysates, Biochemical Journal, 1953b, 53 (3): 366–374, PMC 1198158 , PMID 13032079 .
Sanger, F.; Thompson, E.O.p.; Kitai, R., The amide groups of insulin, Biochemical Journal, 1955, 59 (3): 509–518, PMC 1216278 , PMID 14363129 .
Ryle, A.P.; Sanger, F.; Smith, L.F.; Kitai, R., The disulphide bonds of insulin, Biochemical Journal, 1955, 60 (4): 541–556, PMC 1216151 , PMID 13249947 .
Brown, H.; Sanger, F.; Kitai, R., The structure of pig and sheep insulins, Biochemical Journal, 1955, 60 (4): 556–565, PMC 1216152 , PMID 13249948 .
Sanger, F., Chemistry of Insulin: determination of the structure of insulin opens the way to greater understanding of life processes, Science, 1959, 129 (3359): 1340–1344, Bibcode:1959Sci...129.1340G, PMID 13658959, doi:10.1126/science.129.3359.1340 .
Milstein, C.; Sanger, F., An amino acid sequence in the active centre of phosphoglucomutase, Biochemical Journal, 1961, 79 (3): 456–469, PMC 1205670 , PMID 13771000 .
Marcker, K.; Sanger, F., N-formyl-methionyl-S-RNA, Journal of Molecular Biology, 1964, 8 (6): 835–840, PMID 14187409, doi:10.1016/S0022-2836(64)80164-9 .
Sanger, F.; Brownlee, G.G.; Barrell, B.G., A two-dimensional fractionation procedure for radioactive nucleotides, Journal of Molecular Biology, 1965, 13 (2): 373–398, PMID 5325727, doi:10.1016/S0022-2836(65)80104-8 .
Brownlee, G.G.; Sanger, F.; Barrell, B.G., Nucleotide sequence of 5S-ribosomal RNA from Escherichia coli, Nature, 1967, 215 (5102): 735–736, Bibcode:1967Natur.215..735B, PMID 4862513, doi:10.1038/215735a0 .
Brownlee, G.G.; Sanger, F., Nucleotide sequences from the low molecular weight ribosomal RNA of Escherichia coli, Journal of Molecular Biology, 1967, 23 (3): 337–353, PMID 4291728, doi:10.1016/S0022-2836(67)80109-8 .
Brownlee, G.G.; Sanger, F.; Barrell, B.G., The sequence of 5S ribosomal ribonucleic acid, Journal of Molecular Biology, 1968, 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., Nucleotide sequence from the coat protein cistron of R17 bacteriophage RNA, Nature, 1969, 223 (5210): 1009–1014, Bibcode:1969Natur.223.1009A, PMID 5811898, doi:10.1038/2231009a0 .
Barrell, B.G.; Sanger, F., The sequence of phenylalanine tRNA from E. coli, FEBS Letters, 1969, 3 (4): 275–278, PMID 11947028, doi:10.1016/0014-5793(69)80157-2 .
Jeppesen, P.G.; Barrell, B.G.; Sanger, F.; Coulson, A.R., Nucleotide sequences of two fragments from the coat-protein cistron of bacteriophage R17 ribonucleic acid, Biochemical Journal, 1972, 128 (5): 993–1006, PMC 1173988 , PMID 4566195 .
Sanger, F.; Donelson, J.E.; Coulson, A.R.; Kössel, H.; Fischer, D., 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, 1973, 70 (4): 1209–1213, Bibcode:1973PNAS...70.1209S, PMC 433459 , PMID 4577794, doi:10.1073/pnas.70.4.1209 .
Sanger, F.; Coulson, A.R., A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase, Journal of Molecular Biology, 1975, 94 (3): 441–448, PMID 1100841, doi:10.1016/0022-2836(75)90213-2 .
Sanger, F.; Nicklen, S.; Coulson, A.R., DNA sequencing with chain-terminating inhibitors, Proceedings of the National Academy of Sciences USA, 1977, 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., Nucleotide sequence of bacteriophage φX174 DNA, Nature, 1977, 265 (5596): 687–695, Bibcode:1977Natur.265..687S, PMID 870828, doi:10.1038/265687a0 .
Sanger, F.; Coulson, A.R., The use of thin acrylamide gels for DNA sequencing, FEBS Letters, 1978, 87 (1): 107–110, PMID 631324, doi:10.1016/0014-5793(78)80145-8 .
Sanger, F.; Coulson, A.R.; Barrell, B.G.; Smith, A.J.; Roe, B.A., Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing, Journal of Molecular Biology, 1980, 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., Sequence and organization of the human mitochondrial genome, Nature, 1981, 290 (5806): 457–465, Bibcode:1981Natur.290..457A, PMID 7219534, doi:10.1038/290457a0 .
Anderson, S.; De Bruijn, M.H.; Coulson, A.R.; Eperon, I.C.; Sanger, F.; Young, I.G., Complete sequence of bovine mitochondrial DNA. Conserved features of the mammalian mitochondrial genome, Journal of Molecular Biology, 1982, 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., Nucleotide sequence of bacteriophage λ DNA, Journal of Molecular Biology, 1982, 162 (4): 729–773, PMID 6221115, doi:10.1016/0022-2836(82)90546-0 .
Sanger, F., Sequences, sequences, and sequences, Annual Review of Biochemistry, 1988, 57: 1–28, PMID 2460023, doi:10.1146/annurev.bi.57.070188.000245 .

外部連結

[1] 廖重葳鄭景徽蔡昌樺。Frederick Sanger (1918-)，微生物的世界，東吳大學。

[2] Sanger F, Nicklen S, Coulson AR., DNA sequencing with chain-terminating inhibitors, Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7

[3] Introduction to the Sanger Institute - Sanger Institute

[1]

[2]

[3]

@@ 第49行： / 第49行： @@
 * [http://www.sanger.ac.uk/Info/Intro/sanger.shtml 桑格研究院有關弗雷德里克·桑格的介紹]
 * [http://nobelprize.org/nobel_prizes/chemistry/laureates/1980/sanger-autobio.html 諾貝爾獎官方網站生平介紹]
+==相關文獻==
+<div class='references-small'>
+*{{cite pmid|16747571}}
+*{{cite pmid|16747737}}
+*{{cite pmid|16747948}}
+*{{cite pmid|20344639}}
+*{{cite pmid|16748281}}
+*{{cite pmid|16748471}}
+*{{cite pmid|15396627}}
+*{{citation | last1= Sanger | first1=F. | last2=Tuppy | first2=H. | year=1951a | title= The amino-acid sequence in the phenylalanyl chain of insulin. 1. The identification of lower peptides from partial hydrolysates | journal=Biochemical Journal | volume=49 | issue= 4 | pages=463–481 | pmid=14886310 | pmc=1197535 }}.
+*{{citation | last1= Sanger | first1=F. | last2=Tuppy | first2=H. | year=1951b | title= The amino-acid sequence in the phenylalanyl chain of insulin. 2. The investigation of peptides from enzymic hydrolysates | journal=Biochemical Journal | volume=49 | issue= 4 | pages=481–490 | pmid=14886311 | pmc=1197536 }}.
+*{{citation | last1= Sanger | first1=F. | last2= Thompson | first2=E.O.P. | year=1953a | title= The amino-acid sequence in the glycyl chain of insulin. 1. The identification of lower peptides from partial hydrolysates | journal=Biochemical  Journal | volume=53 | issue= 3 | pages=353–366 | pmid=13032078 | pmc=1198157 }}.
+*{{citation | last1= Sanger | first1=F. | last2= Thompson | first2=E.O.P. | year=1953b | title= The amino-acid sequence in the glycyl chain of insulin. 2. The investigation of peptides from enzymic hydrolysates | journal=Biochemical Journal | volume=53 | issue= 3 | pages=366–374 | pmid=13032079 | pmc=1198158 }}.
+*{{citation | last1=Sanger | first1=F. | last2=Thompson | first2=E.O.p. | last3=Kitai | first3=R. | year=1955 | title=The amide groups of insulin | journal=Biochemical Journal | volume=59 | issue=3 | pages=509–518 | pmid=14363129 | pmc=1216278 }}.
+*{{citation | last1=Ryle | first1=A.P. | last2=Sanger | first2=F. | last3=Smith | first3=L.F. | last4=Kitai | first4=R. | year=1955 | title=The disulphide bonds of insulin | journal=Biochemical Journal | volume=60 | issue=4 | pages=541–556 | pmid=13249947 | pmc=1216151 }}.
+*{{citation | last1=Brown | first1=H. | last2=Sanger | first2=F. | last3=Kitai | first3=R. | year=1955 | title= The structure of pig and sheep insulins | journal=Biochemical Journal | volume=60 | issue=4 | pages=556–565 | pmid=13249948 | pmc=1216152 }}.
+*{{citation | last=Sanger | first=F. | year=1959 | title= Chemistry of Insulin: determination of the structure of insulin opens the way to greater understanding of life processes | journal=Science | volume=129 | pages=1340–1344 | doi=10.1126/science.129.3359.1340 | pmid=13658959 | issue=3359|bibcode = 1959Sci...129.1340G }}.
+*{{citation | last1=Milstein | first1=C. | last2= Sanger | first2=F. | year=1961 | title= An amino acid sequence in the active centre of phosphoglucomutase | journal=Biochemical Journal | volume=79 | pages=456–469 | pmid=13771000 | pmc=1205670 | issue=3 }}.
+*{{citation | last1=Marcker | first1=K. | last2=Sanger | first2=F. | year=1964 | title=''N''-formyl-methionyl-S-RNA | journal=Journal of Molecular Biology | volume=8 | pages=835–840 | pmid=14187409 | doi=10.1016/S0022-2836(64)80164-9 | issue=6 }}.
+*{{citation | last1=Sanger | first1=F. | last2=Brownlee | first2=G.G. | last3=Barrell | first3=B.G. | year=1965 | title= A two-dimensional fractionation procedure for radioactive nucleotides | journal=Journal of Molecular Biology | volume=13 | issue=2 | pages=373–398 | pmid=5325727 | doi=10.1016/S0022-2836(65)80104-8  }}.
+*{{citation | last1=Brownlee | first1=G.G.| last2=Sanger | first2=F. | last3=Barrell | first3=B.G. | year=1967 | title= Nucleotide sequence of 5S-ribosomal RNA from ''Escherichia coli'' | journal=Nature | volume=215 | issue=5102 | pages=735–736 | pmid=4862513 | doi=10.1038/215735a0 |bibcode = 1967Natur.215..735B }}.
+*{{citation | last1=Brownlee | first1=G.G. | last2=Sanger | first2=F. | year=1967 | title= Nucleotide sequences from the low molecular weight ribosomal RNA of ''Escherichia coli'' | journal=Journal of Molecular Biology | volume=23 | issue=3 | pages=337–353 | pmid=4291728 | doi=10.1016/S0022-2836(67)80109-8 }}.
+*{{citation | last1=Brownlee | first1=G.G.| last2=Sanger | first2=F. | last3=Barrell | first3=B.G. | year=1968 | title= The sequence of 5S ribosomal ribonucleic acid | journal=Journal of Molecular Biology | volume=34 | issue=3 | pages=379–412 | pmid=4938553 | doi=10.1016/0022-2836(68)90168-X }}.
+*{{citation | last1=Adams | first1=J.M. | last2=Jeppesen | first2=P.G. | last3=Sanger | first3=F. | last4=Barrell | first4=B.G. | year=1969 | title= Nucleotide sequence from the coat protein cistron of R17 bacteriophage RNA | journal=Nature | volume=223 | issue=5210 | pages=1009–1014 | pmid=5811898 | doi=10.1038/2231009a0 |bibcode = 1969Natur.223.1009A }}.
+*{{citation | last1=Barrell | first1=B.G. | last2=Sanger | first2=F. | year=1969 | title=The sequence of phenylalanine tRNA from ''E. coli'' | journal=FEBS Letters | volume=3 | issue=4 | pages=275–278 | pmid=11947028 | doi=10.1016/0014-5793(69)80157-2 }}.
+*{{citation | last1=Jeppesen | first1=P.G. | last2=Barrell | first2=B.G. | last3=Sanger | first3=F. | last4=Coulson | first4=A.R. | year=1972 | title= Nucleotide sequences of two fragments from the coat-protein cistron of bacteriophage R17 ribonucleic acid | journal=Biochemical Journal | volume=128 | issue=5 | pages=993–1006 | pmid=4566195 | pmc=1173988 }}.
+*{{citation | doi=10.1073/pnas.70.4.1209 | last1=Sanger | first1=F. | last2=Donelson | first2=J.E. | last3=Coulson | first3=A.R. | last4=Kössel | first4=H. | last5=Fischer | first5=D. | year=1973 | title= Use of DNA Polymerase I Primed by a Synthetic Oligonucleotide to Determine a Nucleotide Sequence in Phage f1 DNA | journal=Proceedings of the National Academy of Sciences USA | volume=70 | issue=4 | pages=1209–1213 | pmid=4577794 | pmc=433459 |bibcode = 1973PNAS...70.1209S }}.
+*{{citation | last1=Sanger | first1=F. | last2=Coulson | first2=A.R. | year=1975 | title= A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase | journal=Journal of Molecular Biology | volume=94 | issue=3 | pages=441–448 | pmid=1100841 | doi=10.1016/0022-2836(75)90213-2 }}.
+*{{citation | doi=10.1073/pnas.74.12.5463 | last1=Sanger| first1=F. | last2=Nicklen| first2=S. | last3=Coulson| first3=A.R.|title=DNA sequencing with chain-terminating inhibitors| journal=Proceedings of the National Academy of Sciences USA | year=1977 | volume=74 | issue=12 | pages=5463–5467 | pmid=271968 | pmc=431765 |bibcode = 1977PNAS...74.5463S }}. According to the [[Institute for Scientific Information]] (ISI) database, by October 2010 this paper had been cited over 64,000 times.
+*{{citation | last1=Sanger | first1=F. | last2=Air | first2=G.M. | last3=Barrell | first3=B.G. | last4=Brown | first4=N.L. | last5=Coulson | first5=A.R. | last6=Fiddes | first6=C.A. | last7=Hutchinson | first7=C.A. | last8=Slocombe | first8=P.M. | last9=Smith | first9=M. | year=1977 | title= Nucleotide sequence of bacteriophage φX174 DNA | journal=Nature | volume=265 | issue=5596 | pages=687–695 | pmid=870828 | doi=10.1038/265687a0 |bibcode = 1977Natur.265..687S }}.
+*{{citation | last1=Sanger | first1=F. | last2=Coulson | first2=A.R. | year=1978 | title= The use of thin acrylamide gels for DNA sequencing | journal= FEBS Letters | volume=87 | issue=1 | pages=107–110 | pmid=631324 | doi=10.1016/0014-5793(78)80145-8 }}.
+*{{citation | last1=Sanger |first1=F. | last2=Coulson | first2=A.R. | last3=Barrell | first3=B.G. | last4=Smith | first4= A.J. | last5=Roe | first5=B.A. | year=1980 | title= Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing | journal=Journal of Molecular Biology | volume=143 | issue=2 | pages=161–178 | pmid=6260957 | doi=10.1016/0022-2836(80)90196-5 }}.
+*{{citation | last1=Anderson | first1=S. | year=1981 | last2=Bankier | first2=A.T. | last3=Barrell | first3=B.G. | last4=De Bruijn | first4=M.H. | last5=Coulson | first5=A.R. | last6=Drouin | first6=J. | last7=Eperon | first7=I.C. | last8=Nierlich | first8=D.P. | last9=Roe | first9=B.A. | title= Sequence and organization of the human mitochondrial genome | journal=Nature | volume=290 | issue=5806 | pages=457–465 | pmid=7219534 | doi=10.1038/290457a0 |bibcode = 1981Natur.290..457A }}.
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+</div>
 == 外部連結 ==