(LQOHLWXQJ
[1] Ä7KH1REHO3UL]HLQ&KHPLVWU\3UHVV5HOHDVH³ Nobelprize.org.1REHO0HGLD
$%:HE-XOKWWSZZZQREHOSUL]HRUJQREHOBSUL]HVFKHPLVWU\
ODXUHDWHVSUHVVKWPO!
[2] Ä7KH1REHO3UL]HLQ&KHPLVWU\3RSXODU,QIRUPDWLRQ³ Nobelprize.org.1REHO 0HGLD$%:HE-XOKWWSZZZQREHOSUL]HRUJQREHOBSUL]HVFKHPLVWU\
ODXUHDWHVSRSXODUKWPO!
[3] Ä7KH1REHO3UL]HLQ&KHPLVWU\$GYDQFHG,QIRUPDWLRQ³ Nobelprize.org.1REHO 0HGLD$%:HE-XOKWWSZZZQREHOSUL]HRUJQREHOBSUL]HVFKHPLVWU\
ODXUHDWHVDGYDQFHGKWPO!
[4] 5-/HINRZLW]-5RWK:3ULFHU,3DVWDQ Proc. Natl. Acad. Sci. USA 1970 65 745-752.
[5] 5-/HINRZLW]-5RWK,3DVWDQ Science 1970 170
[6] 5$)'L[RQ%..RELOND'-6WUDGHU-/%HQRYLF+*'RKOPDQ7)ULHOOH 0$%RODQRZVNL&'%HQQHW(5DQGV5('LHKO5$0XPIRUG((6ODWHU ,66LJDO0*&DURQ5-/HINRZLW]&'6WUDGHU Nature 1986 321 [7] 6*)5DVPXVVHQ%7'H9UHH<=RX$&.UXVH.<&KXQJ76.RELOND
)67KLDQ36&KDH(3DUGRQ'&DOLQVNL-00DWKLHVHQ67$6KDK -$/\RQV0&DIIUH\6+*HOOPDQ-6WH\DHUW*6NLQLRWLV:,:HLV
5.6XQDKDUD%..RELOND Nature 2011KWWSG[GRLRUJQDWXUH [8] *&DVL'+LOYHUW Curr. Opin. Struct. Biol. 2003 13
[9] '6FKZDU]HU3$&ROH Curr. Opin. Struct. Biol. 2005 9 [10] 8$UQROG Biotechnol. Lett. 2009 31
Stand der Forschung
[11] 0%HUJPDQQ/=HUYDV Ber. Dtsch. Chem. Ges. 1932 65 [12] /$&DUSLQR*<+DX J. Am. Chem. Soc. 1970 92
[13] 7:LHODQG:.HUQ56HKULQJ Justus Liebigs Ann. Chem. 1950 596 [14] -&6KHHKDQ*3+HVV J. Am. Chem. Soc. 1955 77
[15] :.|QLJ5*HLJHU Chem. Ber. 1970 103 [16] )$OEHULFLR Curr. Opin. Struct. Biol. 2004 8 [17] 5%0HUULH¿HOG J. Am. Chem. Soc. 1963 85
[18] %%DGHU..XKQ'-2ZHQ+:DOGPDQQ$:LWWLQJKRIHU-.XKOPDQQ Nature 2000 403
[19] &35+DFNHQEHUJHU'6FKZDU]HU Angew. Chem. Int. Ed. 2008 47 [20] -37DP=0LDR J. Am. Chem. Soc. 1999 121
[21] -37DP-;X.'(RP Biopolymers 2001 60
[22] 5+XLVJHQ*6]HLPLHV/0|ELXV Chem. Ber. 1967 100
[23] +&.ROE0*)LQQ.%6KDUSOHVV Angew. Chem. 2001 113
[24] 995RVWRYWVHY/**UHHQ99)RNLQ.%6KDUSOHVV Angew. Chem. 2002 114 2708-2711.
[25] 7:LHODQG(%RNHOPDQQ/%DXHU+8/DQJ+/DX Justus Liebigs Ann. Chem.
1953 583
[26] '6.HPS Biopolymers 1981 20
[27] 3('DZVRQ7:0XLU,&ODUN/HZLV6%+.HQW Science 1994 266 [28] -37DP<$/X&)/LX-6KDR Proc. Natl. Acad. Sci. USA 1995 92
12485-12489.
[29] 3('DZVRQ6%+.HQW Annu. Rev. Biochem 2000 69
[30] 70+DFNHQJ-+*ULI¿Q3('DZVRQ Proc. Natl. Acad. Sci. USA 1999 96 10068-10073.
[31] 6%+.HQW Chem. Soc. Rev. 2009 38
[32] ;/L7.DZDNDPL6$LPRWR Tetrahedron Lett. 1998 39
[33] *:.HQQHU-50F'HUPRWW5&6KHSSDUG Chem. Commun. 1971 [34] %-%DFNHV-$(OOPDQ J. Org. Chem. 1999 64
[35] 5,QJHQLWR(%LDQFKL')DWWRUL$3HVVL J. Am. Chem. Soc. 1999 121 [36] <6KLQ.$:LQDQV%-%DFNHV6%+.HQW-$(OOPDQ&5%HUWR]]L J. Am.
Chem. Soc. 1999 121
[37] '6ZLQQHQ'+LOYHUW Org. Lett. 2000 2
[38] $6HZLQJ'+LOYHUW Angew. Chem. Int. Ed. 2001 40
[39] 7.DZDNDPL06XPLGD.1DNDPXUD79RUKHUU6$LPRWR Tetrahedron Lett. 2005 46
[40] 12OOLYLHU-%%HKU2(O0DKGL$%ODQSDLQ20HOQ\N Org. Lett. 2005 7 2647-2650.
[41] .1DNDPXUD+0RUL7.DZDNDPL++RMR<1DNDKDUD6$LPRWR Int. J. Pept. Res.
Ther. 2007 13
[42] )0HQGH26HLW] Angew. Chem. 2007 119
[43] )0HQGH0%HLVVZHQJHU26HLW] J. Am. Chem. Soc. 2010 132 [44] 5YRQ(JJHONUDXW*RWWDQND$.ORVH$*%HFN6LFNLQJHU0%H\HUPDQQ
Tetrahedron Lett. 2003 44
[45] 6)XWDNL.6RJDZD-0DUX\DPD7$VDKDUD01LZD Tetrahedron Lett. 1997 38 6237-6240.
[46] /(&DQQH3%RWWL5-6LPRQ<&KHQ($'HQQLV6%+.HQW J. Am. Chem.
Soc. 1999 121
[47] $%ULN(.HLQDQ3('DZVRQ J. Org. Chem. 2000 65 [48] 7+DDFN00XWWHU Tetrahedron Lett. 1992 33
[49] '%DQJ6%+.HQW Angew. Chem. 2004 116
[50] 9<7RUEHHY6%+.HQW Angew. Chem. 2007 119
[51] '%DQJ%/3HQWHOXWH6%+.HQW Angew. Chem. 2006 118
[52] +0DR6$+DUW$6FKLQN%$3ROORN J. Am. Chem. Soc. 2004 126 [53] 63ULW]<:ROI2.UDHWNH-.ORVH0%LHQHUW0%H\HUPDQQ J. Org. Chem. 2007
72
[54] +7RQ7KDW*/LX6.0D]PDQLDQ.))DXOO26FKQHHZLQG Proc. Natl. Acad.
Sci. USA 1999 96
[55] /$0DUUDI¿QL$&'H'HQW26FKQHHZLQG Microbiol. Mol. Bio. Rev. 2006 70 192-221.
[56] 5*.UXJHU%2WYRV%$)UDQNHO0%HQWOH\3'RVWDO'*0F&DIIHUW\
Biochemistry 2004 43
[57] ,6FKHFKWHU$%HUJHU Biochem. Biophys. Res. Commun. 1967 27
[58] .3LRWXNK%*HOWLQJHU1+HLQULFK)*HUWK0%H\HUPDQQ&)UHXQG'6FKZDU]HU J. Am. Chem. Soc 2011 133
[59] %/1LOVVRQ0%6RHOOQHU575DLQHV Annu. Rev. Biophys. Biomol. Struct. 2005 34
[60] 04;X)%3HUOHU EMBO J. 1996 15
[61] 7:0XLU'6RQGKL3$&ROH Proc. Natl. Acad. Sci. USA 1998 95 [62] 04;X7&(YDQV-U Methods 2001 24
[63] %%ULDQG Dissertation+XPEROGW8QLYHUVLWlW]X%HUOLQ 2009.
[64] 6$EHO Diplomarbeit+XPEROGW8QLYHUVLWlW]X%HUOLQ 2009.
[65] 63ULW]2.UDHWNH$.ORVH-.ORVH65RWKHPXQG.)HFKQHU0%LHQHUW 0%H\HUPDQQ Angew. Chem. Int. Ed.2008 47
[66] 63ULW] Dissertation+XPEROGW8QLYHUVLWlW]X%HUOLQ 2008.
[67] &+7ULQK'36PLWK$3.DOYHUGD6(93KLOOLSV6(5DGIRUG Proc. Natl.
Acad. Sci. USA 2002 99
[68] 3-%MRUNPDQ0$6DSHU%6DPUDRXL:6%HQQHWW-/6WURPLQJHU'&:LOH\
Nature 1987 329
[69] 6<DPDPRWR--.D]DPD,1DULWD+1DLNL)*HM\R Bone 2009 4566 [70] +(:KLWH-/+RGJNLQVRQ75-DKQ6&RKHQ.UDXV]:6*RVDO60OOHU
(92UORYD6(5DGIRUG+56DLELO J. Mol. Biol. 2009 389
[71] )*HM\R7<DPDGD62GDQL<1DNDJDZD0$UDNDZD7.XQLWRPR+.DWDRND 06X]XNL<+LUDVDZD76KLUDKDPD$6&RKHQ.6FKPLG Biochem. Biophys. Res.
Commun. 1985 129
[72] '9%ODKR$'0LUDQNHU Biochemistry 2009 48
[73] 9-0F3DUODQG10.DG$3.DOYHUGD$%URZQ3.LUZLQ-RQHV0*+XQWHU 06XQGH6(5DGIRUG Biochemistry 2000 39
[74] &-0RUJDQ0*HOIDQG&$WUH\D$'0LUDQNHU J. Mol. Biol. 2001 309
[75] 6/0\HUV6-RQHV75-DKQ,-0RUWHQ*$7HQQHQW(:+HZLWW
6(5DGIRUG Biochemistry 2006 45
[76] +)DELDQ&6FKXOW]-%DFNPDQQ8+DKQ:6DHQJHU++0DQWVFK'1DXPDQQ Biochemistry 1994 33
[77] 67UHPPHO0%H\HUPDQQ+2VFKNLQDW0%LHQHUW'1DXPDQQ+)DELDQ Angew.
Chem. 2005 117
[78] +)DELDQ.*DVW0/DXH50LVVHOZLW]%8FKDQVND=LHJOHU$=LHJOHU '1DXPDQQ Biochemistry 2008 47
[79] -&6SHW]OHU7+RHJ-HQVHQ Bioorg. Med. Chem. 2007 15 [80] *&DVL'+LOYHUW J. Biol. Chem. 2007 282
[81] 55|GHU.%UXQV$6KDUPD$(LVVPDQQ)+DKQ16WXGWUXFNHU7)RVVHQ 9:UD\3+HQNOHLQ86FKXEHUW J. Pept. Sci. 2008 14
[82] *&DVL*5RHOIHV'+LOYHUW ChemBioChem 2008 9
[83] %%ULDQG1.RW]XU9+DJHQ0%H\HUPDQQ Tetrahedron Lett. 2008 49 [84] =)LGDQ$<RXQLV36FKPLHGHU59RONPHU J. Pept. Sci. 2011 17 [85] $0RVFR9=ODWHY&*XDUQDFFLD63RQJRU$&DPSDQHOOD6=DKDULHY
3**LXOLDQLQL PLoS ONE 2012 7H
[86] 7:|KU00XWWHU Tetrahedron Lett. 1995 36
[87] 7:|KU):DKO$1HI]L%5RKZHGGHU76DWR;6XQ00XWWHU J. Am. Chem.
Soc. 1996 118
[88] (1LFROiV(3HGURVR(*LUDOW Tetrahedron Lett. 1989 30
[89] 5'|OOLQJ0%H\HUPDQQ-+DHQHO).HUQFKHQ(.UDXVH3)UDQNH0%UXGHO 0%LHQHUW J. Chem. Soc. Chem. Commun. 1994
[90] -&HEUӽQ9'RPLQJR)5HLJ J. Peptide Res. 2003 62
[91] 00HUJOHU)'LFN%6D[&6WlKHOLQ79RUKHUU J. Peptide Sci. 2003 9 [92] 70LFKHOV5'|OOLQJ8+DEHUNRUQ:0LHU Org. Lett. 2012 14 [93] *+EHQHU:*|KULQJ+-0XVLRO/0RURGHU Peptide Res. 1992 5 [94] 5/1REOH'<DPDVKLUR&+/L J. Am. Chem. Soc. 1976 98 [95] 0%LHQHUW(.ODXVFKHQ].1LNROLFV+1LHGULFK Int. J. Peptide Res. 1982 19
310-314.
[96] 5&KHQ.$/HZLV0+3HUULQ::9DOH Proc. Natl. Acad. Sci. USA 1993 90 8967-8971.
[97] 5-/HINRZLW] Cell 1993 74
[98] /2OLYHLUD$&03DLYD&6DQGHU*9ULHQG Trends Pharmacol. Sci. 1994 15 170-172.
[99] +(+DPP J. Biol. Chem. 1998 273
[100] -9DXJKDQ&'RQDOGVRQ-%LWWHQFRXUW0+3HUULQ./HZLV66XWWRQ5&KDQ
$97XUQEXOO'/RYHMR\&5LYLHU-5LYLHU3(6DZFKHQNR:9DOH Nature 1995 378
[101] '(*ULJRULDGLV;-/LX-9DXJKQ6)3DOPHU&'7UXH::9DOH1/LQJ (%'H6RX]D Mol. Pharmacol 1996 50
[102] )+ROVERHU Spektrum der Wissenschaft 1993 5
[103] 0+3HUULQ&-'RQDOGVRQ5&KHQ.$/HZLV::9DOH Endo. 1993 133 3058-3061.
[104] (%'H6RX]D Psychoneuroendocrinology 1995 20
[105] 0+3HUULQ66XWWRQ'/%DLQ:7%HUJJUHQ::9DOH Endo. 1998 139 566-570.
[106] 0+3HUULQ:+)LVFKHU.6.XQLWDNH$*&UDLJ6&.RHUEHU/$&HUYLQL -(5LYLHU-&*URSSH-*UHHQZDOG601LHOVHQ::9DOH J. Biol. Chem. 2001 276
[107] -.ORVH.)HFKQHU0%H\HUPDQQ(.UDXVH1:HQGW0%LHQHUW55XGROSK 65RWKHPXQG Biochemistry 2005 44
[108] 00XWWHU69XLOOHXPLHU Angew. Chem. 1989 101
[109] 00XWWHU3'XP\3*DUURXVWH&/HKPDQQ00DWKLHX&3HJJLRQ63HOXVR
$5D]DQDPH*7XFKVFKHUHU Angew. Chem. 1996 108
[110] /-4L$7/HXQJ<;LRQJ.$0DU[$%$ERX6DPUD Biochemistry 1997 36 12442-12448.
[111] 0%H\HUPDQQ1+HLQULFK.)HFKQHU-)XUNHUW:=KDQJ2.UDHWNH0%LHQHUW +%HUJHU Br. J. Pharmacol. 2007 151
=LHOVWHOOXQJ
[112] '-%RHUHPD9$7HUHVKNR6%+.HQW Biopolymers 2008 90
(UJHEQLVVH 'LVVNXVLRQ
[113] 3('DZVRQ0-&KXUFKLOO05*KDGLUL6%+.HQW J. Am. Chem. Soc. 1997 119
[114] )$OEHULFLR,$QQLV05R\R*%DUDQ\20033UHSDUDWLRQDQGKDQGOLQJRISHSWLGHV containing methionine and cysteine in: Fmoc Solid Phase Peptide Synthesis: A practical approach HGV:&&KDQ3':KLWHSS
[115] /&/DQH Anal. Biochem. 1978 86
[116] ::DOFKHU+7ROO$,QJHQGRK&*+XEHU J. Chromatogr. A 2004 1053 [117] +/LX%;X0.5D\=6KDKURNK J. Chromatogr. A 2008 1210
[118] -&*HVTXLHUH('LHVLV07&XQJ$7DUWDU J. Chromatogr. A 1989 478 [119] :5*UD\-(5LYLHU5*DO\HDQ/-&UX]%02OLYHUD J. Biol. Chem. 1983 258
12247-12251.
[120] 71LVKLNDZD<+D\DVKL66X]XNL+.XER+2KWDQL Anal. Sci. 1996 12 [121] 0'LWWPDQQ06DGHN56HLGHO0(QJHOKDUG J. Pept. Sci 2012 18 [122] *%DUDQ\5%0HUULH¿HOG1980$QDO\VLV6\QWKHVLVDQG%LRORJ\LQ The Peptides
HGV(*URVV-0HLHQKRIHU9RO$FDGHPLF3UHVV1HZ<RUNSSXQGGHUHQ 5HIHUHQ]HQ
[123] &+DQD\ Dissertation+XPEROGW8QLYHUVLWlW]X%HUOLQ 1998.
[124] 0*RRGPDQ//HYLQH J. Am. Chem. Soc. 1964 86
[125] &*ULHKO$.ROEH60HUNHO-&KHP6RF3HUNLQ7UDQV 1996 11 [126] (&%-RKQVRQ6%+.HQW J. Am. Chem. Soc. 2006 128
[127] 77HUX\D77DQDND7.DZDNDPL.$NDML6$LPRWR J. Pept. Sci. 2012 18 [128] '/6WDOOLQJ**LOOH&:*HKUNH Anal. Biochem. 1967 18
[129] 3+XãHN.0DFHN J. Chromatogr. A 1975 113 [130] +%UFNQHU'%HFNHU0/SNH Chirality 1993 5
[131] +)UDQN::RLZRGH*1LFKROVRQ(%D\HU Liebigs Ann. Chem. 1981 1981 354-365.
[132] :&-RKQVRQ-U Ann. Rev. Biophys. Biophys. Chem. 1988 17 [133] -73HOWRQ/50F/HDQ Anal. Biochem. 2000 277
[134] 60.HOO\7--HVV1&3ULFH Biochim. Biophys. Acta 2005 1751 [135] <2KKDVKL<+DJLKDUD*.R]KXNK0+RVKLQR.+DVHJDZD,<DPDJXFKL
+1DLNL<*RWR J. Biochem. 2002
[136] 5&+LOOLJ3*&RXOLH96WURREDXW:6DHQJHU$=LHJOHU0+OVPH\HU J. Mol.
Biol. 2001 310
[137] 0*R]X<+/HH<2KKDVKL0+RVKLQR+1DLNL<*RWR J. Biochem. 2003 133 731-736.
[138] 1HZ(QJODQG%LR/DEV,03$&77:,1,QVWUXFWLRQ0DQXDO Catalog #E6950S Version 1.4 1/06.
[139] ':LHWIHOG1+HLQULFK-)XUNHUW.)HFKQHU0%H\HUPDQQ0%LHQHUW+%HUJHU J. Biol. Chem. 2004 279
=XVDPPHQIDVVXQJ $XVEOLFN
[140] 6%+.HQW Ann. Rev. Biochem. 1988 57
[141] 5&GH/0LOWRQ6&)0LOWRQ3$$GDPV J. Am. Chem. Soc. 1990 112 6039-6046.
[142] ,&RLQ0%H\HUPDQQ0%LHQHUW Nat. Protoc. 2007 2
([SHULPHQWHOOHU7HLO
[143] 83LDQWLQL2:6RUHQVHQ55(UQVW J. Am. Chem. Soc. 1982 104 [144] $$%RWKQHU%\5/6WHSKHQ-0/HH&':DUUHQ5:-HDQOR] J. Am. Chem.
Soc. 1984 106
[145] $%D['*'DYLV J. Magn.Reson. 1985 63
[146] $%D[5+*ULIIH\%/+DZNLQV J. Am. Chem. Soc. 1983 105 [147] $%D[66XEUDPDQLDQ J. Magn. Reson. 1986 67
[148] /(&DPPLVK6$.DWHV2003,QVWUXPHQWDWLRQIRUDXWRPDWHGVROLGSKDVHSHSWLGH synthesis in: Fmoc Solid Phase Peptide Synthesis: A practical approach HGV:&
&KDQ3':KLWHSS
[149] *6FKQRUUHQEHUJ+*HUKDUGW Tetrahedron 1989 45
[150] :&&KDQJ3':KLWH2003%DVLFSURFHGXUHVLQ Fmoc Solid Phase Peptide Synthesis: A practical approach HGV:&&KDQ3':KLWHSS
[151] (.DLVHU5/&ROHVFRWW&'%RVVLQJHU3,&RRN Anal. Biochem. 1970 34 595-598.
[152] .%DUORV'*DWRV-.DOOLWVLV*3DSDSKRWLX36RWLULX<:HQTLQJ:6FKlIHU Tetrahedron Lett. 1989 30
[153] 3URPHJD6HTXHQFLQJ*UDGH0RGL¿HG7U\SVLQ3URWRFRO Literature #9PIV5115HYLVHG 12/11.
[154] 5+RXVVLQ-3RPPHU\0&6DODQ6'HZHHU-)*RRVVHQV3&KDYDWWH -3+QLFKDUW J. Med. Chem. 2002 456XSSRUWLQJ,QIRUPDWLRQ
[155] */RLGO)'LFN00HUJOHU526FKRHQOHEHU Adv. Exp. Med. Biol. 2009 611 163-164.
[156] 0$:DUG7(0F&DUWK\-61LVKLPXUD Anal. Biochem. 1967 20