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specificity




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domainPeptide catalyst withhigh substrate specificity

OH

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Modular assembly

+



O

O

35-mer peptide
O

O

O

O

N

+ H

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O

O

O

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COOH
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7

EMFT7(g¶!8QDUQl0RCS8QDUQl7·u4KIAD*;P>LU&$±²¡»)@<&$f4(*Wn%"!OJQevyc(f4!/(*N
FLU&$±4KIAD.Ñr1,ËÌr)O9HOPU7d &:EMF
T7&4Ã&Ó¦4*Ò¦-)O9HOPU)¿h7®3¾ÌËr)?=CT&:EMFT74±7 #KIAD

ÈqÍÉ7g¶!)KIAD*NFLU&$±²¡»(@<&$Zh?=CTºy^&)l(13OJQev7²¡»(yc4)(4&%!ÎÉÈqÎÉ)KIAD*Àz)l·u)1(    l7hÁ46%*'Àz&*'4l7£2{°)·u%4&¸4
Libraries (first generation)
CXXXXXXXCXXXXXXX
XXXXXXXXXXXX
Selection
Sequences of peptides
CHNHQKATCAAVAKPPVSVQTKYNPLGAKLAAMDAKNSPASADLPIPTTKLGRS

Libraries (third generation)
CHNHQKATCTAQAQSXXXXXXCHNHQKATCRRMRSRXXXXXXCHNHQKATCSWVLVPXXXXXXCHNHQKATCPRDRHGXXXXXXNPLGAKLAGVFWWXXXXXXNPLGAKLAMAMWGXXXXXX

Libraries (second generation)
CHNHQKATCXXXXXXAAVAKPPXXXXXXXXXXXXAAVAKPPVSVQTKYXXXXXXXXXXXXVSVQTKY
NPLGAKLXXXXXXXXXXXXNPLGAKLAAMDAKNSPASAXXXXXXXXXXXXAAMDAKNSPASADLPIPTTKLGRSXXXXXXXXXXXXDLPIPTTKLGRS

Selection
Sequences of peptides that bound to the diketone
CHNHQKATCRRMRSRETSVKK (rpf1368)

Selection

NPLGAKLAGVFWWGQTPGG

Sequences of peptides that bound to the diketone
CHNHQKATCTAQAQS
CHNHQKATCRRMRSR
CHNHQKATCSWVLVP
CHNHQKATCPRDRHG
NPLGAKLAGVFWWNPLGAKLAMAMWG

qÍÊ?=CT&:EMFT74KIAD74)(_!KIADO9HOPU

21-mer peptide protein of interest

21-mer peptide protein of interest
Lys

Lys NH2
O

NH O

O
R

R
R = Labeling compoundsqÎÊ:EMFT74KIAD7@<&$²¡»(OJQ7yc4   jwl)Â´7½Á¨k(d4*O9HOPU2)Ç·u)i¢ª·uÅ)
)¼§(%4 %l4&³b}|sh4LR9MDºy^7$:EMTÈqÏÉ)7f
(14©©¬m~l)Â´7³b)sh(13d47Ä !ÏÉ4&(13·u):EMT±7½Á(¹a%!ÐÉ)*^·u1,KIAD·u(14­µX%)l)Â´)d]ev8MT7·u&4uX%)ml(i'·u1,l[)ª§(i%"!`+52)³bx(14lÂ´)¹a7
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O

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highly fluorescent

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CO2Et

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CO2H

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CO2H
N
H
R1
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O

PMP

R2
Ketones

+

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N

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CO2Et anti-selective

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R

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CO2Et   No.28 (2008 October)9 
[9]\=82?@6[9#aD CM <e[9J@6[9#5;
CM[9#0/L Q^#T*   =8<L@g'&$%@ XO_@[90Z 3W VhbSHW#+.:FH14KY

EI#cN (>! A7bSY2?HGd" A7)E#U4" -!FH4BIXO_aDP,f2?XO_@ '&$%@[9RcN `
V 

  
1) Tanaka, F.; Fuller, R.; Shim, H.; Lerner, R. A.; Barbas, C. F., III. J. Mol. Biol. 2004, 335, 1007-1018.
2) Tanaka, F.; Fuller, R.; Barbas, C. F., III. Biochemistry 2005, 44, 7583-7592.
3) Tanaka, F.; Barbas, C. F., III. J. Am. Chem. Soc. 2002, 124, 3510-3511.
4) Tanaka, F.; Fuller, R.; Asawapornmongkol, L.; Warsinke, A.; Gobuty, S.; Barbas, C. F., III. Bioconjugate Chem. 2007, 18,
1318-1324.
5) Tanaka, F.; Thayumanavan, R.; Barbas, C. F., III. J. Am. Chem. Soc. 2003, 125, 8523-8528.
6) Tanaka, F.; Thayumanavan, R.; Mase, N.; Barbas, C. F., III. Tetrahedron Lett. 2004, 45, 325-328.
7) (a) Mase, N.; Tanaka, F.; Barbas, C. F., III. Org. Lett. 2003, 5, 4369-4372. (b) Mase, N.; Tanaka, F.; Barbas, C. F., III.
Angew. Chem., Int. Ed. 2004, 43, 2420-2423. (c) Mase, N.; Thayumanavan, R.; Tanaka, F.; Barbas, C. F., III. Org. Lett.
2004, 6, 2527-2530.
8) Tanaka, F.; Mase, N.; Barbas, C. F., III. J. Am. Chem. Soc. 2004, 126, 3692-3693.
9) (a) Mitsumori, S.; Zhang, H.; Cheong, P. H.-C.; Houk, K. N.; Tanaka, F.; Barbas, C. F., III. J. Am. Chem. Soc. 2006, 128,
1040-1041. (b) Zhang, H.; Mifsud, M.; Tanaka, F.; Barbas, C. F., III. J. Am. Chem. Soc. 2006, 128, 9630-9631. (c) Zhang,H.; Mitsumori, S.; Utsumi, N.; Imai, M.; Garcia-Delgado, N.; Mifsud, M.; Albertshofer, K.; Cheong, P. H.-Y.; Houk, K. N.;
Tanaka, F.; Barbas, C. F., III. J. Am. Chem. Soc. 2008, 130, 875-886.
10) Tanaka, F. The Chemical Record 2005, 5, 276-285.

   No.28 (2008 October)10

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   No.28 (2008 October)17

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16. Lin, C.-W., Ting, A. Y., J. Am. Chem. Soc., 128, 4542-4543 (2006).

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F. Fan, B. F. Binkowski, B. L. Butler, P. F. Stecha, M. K. Lewis, and K. V. Wood, ACS Chem. Biol., 3,
346-351 (2008).
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[1] Luisi, P.L., Walde, P. Giant Vesicles; John Wiley & Sons Ltd: Chichester (2000).
[2] Angelova, M.I., Soléau, S., Méléard, Ph., Faucon, J.F., Bothorel, P. Progr. Colloid Polym. Sci., 89,
127-131 (1992).
[3] Magome, N., Takemura, T., Yoshikawa, K. Chem. Lett., 26, 205-206 (1997).
[4] Yamada, N.L., Hishida, M., Seto, H., Tsumoto, K., Yoshimura T. Europhys. Lett., 80, 48002 (2007).
[5] Yamashita, Y., Oka, M., Tanaka, T., Yamazaki, M. Biochim. Biophys. Acta, 1561, 129-134 (2002).
[6] Akashi, K., Miyata, H., Itoh, H., Kinoshita, K.Jr. Biophys. J., 74, 2973-2982 (1998).
[7] Yamada, A., Yamanaka, T., Hamada, T., Hase, M., Yoshikawa, K., Baigl, D. Langmuir, 22, 9824-9828(2006).
[8] Pautot, S., Frisken, B.J., Weitz, D.A. Proc. Natl. Acad. Sci. U.S.A., 100, 10718-10721 (2003).
[9] Evans, E., Rawicz, W. Phys. Rev. Lett., 64, 2094-2097 (1990).
[10] Hamada, T., Miura, Y., Ishii, K., Araki, S., Yoshikawa, K., Vestergaard, M., Takagi, M. J. Phys. Chem. B,
111, 10853-10857 (2007).
[11] Nomura, S.M., Tsumoto, K., Hamada, T., Akiyoshi, K., Nakatani, Y., Yoshikawa, K. ChemBioChem, 4,1172-1175 (2003).

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