ChemComm
COMMUNICATION
DOI: 10.1039/C6CC07891E
Journal Name
α
Peptide- thioester
Deprotection Isolated yield
8
9
(
a
) J.B. Blanco-Canosa and P.E. Dawson, Angew. Chem. Int. Edit.
2008, 47(36), 6851; ( ) J.B. Blanco-Canosa, B. Nardone, F. Albericio
and P.E. Dawson, J. Am. Chem. Soc., 2015, 137(22), 7197; ( ) G.
Fang, J. Wang and L. Liu, Angew. Chem. Int. Edit., 2012, 51(41),
,
α
b
GHRH- COSR
GHRH- COSR
HF
47%
44%
α
TFMSA “flow”
c
α
MLKMKTTFY- COSR
MLKMKTTFY- COSR
MLKMKTTFY- COSR
HF
43%
49%
46%
1
0347.
α
TFMSA “flow”
TFMSA “batch”
(a
) M. Murakami, R. Okamoto, M. Izumi and Y. Kajihara, Angew.
α
Chem. Int. Ed., 2012, 51(15), 3567; (b) M. Izumi, M. Murakami, R.
α
ACNRVYIHPFW- COSR
HF
23%
29%
Okamoto and Y. Kajihara, J. Pept. Sci, 2014, 20(2), 98. (c) R. Raz, F.
Burlina, M. Ismail, J. Downward, J. Li, S. J. Smerdon, M. Quibell, P.
D. White and J. Offer, Angew. Chem. Int. Edit., 2016, 55, published
on line. DOI: 10.1002/anie.201607657; (d) P. Thapa, C. C. Cabalteja,
E. E. Philips III, M. J. Espiritu, S. Peigneur, B. G. Mille, J. Tytgat, T.
R. Cummins, J. Bingham, Biopolymers, 2016, 106(5), 737-745.
α
ACNRVYIHPFW- COSR TFMSA “flow”
α
Crambin 1-15- COSR
Crambin 1-15- COSR
Crambin 1-15- COSR
HF
79%
79%
74%
α
TFMSA “flow”
TFMSA “batch”
α
α
Crambin 16-25- COSR
Crambin 16-25- COSR
Crambin 16-25- COSR
HF
85%
78%
78%
1
0 (
a
) H. Yajima, N. Fujii, H. Ogawa and H. Kawatani, J. Chem. Soc.
) H. Yajima and N. Fujii in The
α
TFMSA “flow”
TFMSA “batch”
Chem. Comm., 1974, (3), 107; (
b
α
Peptides: Analysis, Synthesis, Biology, Vol. 5: Special Methods in
Peptide Synthesis, Part B, ed. E. Gross and J. Meienhofer, Academic
Press, New York, New York, 1983, 65-109.
α
α
Crambin 32-46- COSR
Crambin 32-46- COSR
Crambin 32-46- COSR
HF
79%
74%
75%
TFMSA “flow”
TFMSA “batch”
α
α
11 G.N. Jubilut, E. M. Cilli, M. Tominaga, A. Miranda, Y. Okada, and
Table 3. Isolated yields of peptide- thioesters obtained from comparative
deprotection/nucleophilic cleavage experiments. Crude reaction mixtures were
de-salted by solid phase extraction (Grace-Vydac C18 cartridges), and lyophilized
to yield the peptide-α
C. R. Nakaie, Chem. Pharm. Bull., 2001, 49(9), 1089.
th
1
1
2 J Bergot, R.F. Noble and T. Geiser in Peptides 1986: Proc. 19 Eur.
Pept. Symp., ed. D. Theodoropoulos, de Gruyter, Berlin, 1987, 97.
3 S.B.H. Kent, A.R. Mitchell, M. Engelhard and R.B. Merrifield, P.
Natl. Acad. Sci. USA, 1979, 76(5), 2180.
thioesters as stable, non-hygroscopic powders.
Notes and references
a
Department of Chemistry, University of Chicago, Chicago, IL 60637,
1
1
4 H. Yajima and N. Fujii, J. Am. Chem. Soc., 1981, 103(19), 5867.
5 H. Yajima, M. Takeyama, J. Kanaki, O. Nishimura and M. Fujino,
Chem. Pharm. Bull., 1978, 26(12), 3752.
Present Address: Department of Chemistry, Massachusetts Institute of
b
1
6 (
Shinagawa, J. Chem. Soc. Chem. Comm., 1976
N. Fujii, H. Ogawa, H. Yajima, M. Fujino and S. Shinagawa, Chem.
Pharm. Bull., 1977, 25(11), 2929; ( ) Y. Kiso, K. Ito, S. Nakamura,
K. Kitagawa, T. Akita, and H. Moritoki, Chem. Pharm. Bull., 1979,
(6), 1472; ( ) Y. Kiso, S. Nakamura, K. Ito, K. Ukawa, K.
Kitagawa, T. Akita and H. Moritoki, J. Chem. Soc. Chem. Comm.
1979, (21), 971; (
Chem. Comm., 1980, (3), 101.
a
) H. Irie, N. Fujii, H. Ogawa, H. Yajima, M. Fujino and S.
†
Unlike HF, TFMSA remains strongly acidic in aqueous solution, and
,
(22), 922; ( ) H. Irie,
b
upon storage can cause degradation of lyophilized peptides derived from
ether precipitation from TFMSA/TFA mixtures. On-resin deprotection
minimizes this issue, and streamlines the separation of peptide products
from deprotection reactants (which is a hazardous procedure, even for
TFA deprotection/cleavage following Fmoc SPPS).
c
27
d
†
† One observed side reaction not due to the use of alternative
protecting groups was trifluoroacetylation, which reproducibly occurred
to varying extent for N-terminal Ser and Thr peptides. This known side
reaction could be eliminated by acetylation of the N-terminus prior to
,
,
2
3
e
) Y. Kiso, K. Ukawa and T. Akita, J. Chem. Soc.
side chain deprotection (see SI, Figures S9, S10). Where a free N-
terminus Ser or Thr is required, use of a protecting group, stable to 17 Lys(Cl-Z): B.W. Erickson and R.B. Merrifield, J. Am. Chem. Soc.
TFMSA deprotection, and subsequently removable under different
conditions is recommended.
1
973, 95(11), 3757; Tyr(Br-Z): K. Rosenthal, A. Karlström and A.
Undén, Tetrahedron Lett., 1997, 38(6), 1075.
1
8 M. Taichi, T. Kimura and Y. Nishiuchi, Int. J. Pept. Res. Ther., 2009,
15(4), 247.
Electronic Supplementary Information (ESI) available: Experimental
details, LC-MS chromatograms/spectra, and supporting data tables. See
DOI: 10.1039/c000000x/
1
2
9 S.B.H. Kent, Annu. Rev. Biochem., 1988, 57, 957.
0 Preparation of aminomethyl copoly(styrene-1% divinylbenzene)
resin: P.W.R. Harris, S.H. Yang and M.A. Brimble, Tetrahedron
Lett., 2011, 52(45), 6024; Grafting of aminomethyl copoly(styrene-
1
2
3
S.B.H. Kent, Chem. Soc. Rev., 2009, 38(2), 338.
P.E. Dawson and S.B.H. Kent, Annu. Rev. Biochem., 2000, 69, 923.
(a
) M. Schnölzer, P. Alewood, A. Jones, D. Alewood and S.B.H.
Kent, Int. J. Pept. Prot. Res., 1992, 40(3-4), 180; ( ) M. Schnölzer, P.
b
1
% divinylbenzene) resin: S. Zalipsky, J.L. Chang, F. Albericio and
Alewood, A. Jones, D. Alewood and S.B.H. Kent, Int. J. Pept. Res.
Ther., 2007, 13(1-2), 31.
G. Barany, React. Polym., 1994, 22(3), 243.
2
1 S. Markos, A. Saravanos, M. Batistatos, A. Aletras, D. Gatos and K.
Barlos in Understanding Biology Using Peptides, ed. S.E. Blondelle,
Springer, New York, 2006, 140.
4
5
T.M. Hackeng, J.H. Griffin and P.E. Dawson, P. Natl. Acad. Sci.
USA, 1999, 96(18), 10068.
(a
) S. Sakakibara and Y. Shimonishi, B. Chem. Soc. Jpn., 1965,
(8), 1412; ( ) S. Sakakibara, Y. Shimonishi, Y. Kishida, M. Okada
2
2
2 W. Zeng, P. Regamey, K. Rose, Y. Wang and E. Bayer, J. Pept. Res.
997, 49(3), 273.
3 G. Hubener, W. Gohring, H.J. Musiol and L. Moroder, Peptide Res.
992, (5), 287.
,
38
b
1
and H. Sugihara, B. Chem. Soc. Jpn., 1967, 40(9), 2164.
,
6
7
J. Lenard and A.B. Robinson, J. Am. Chem. Soc., 1967, 89(1), 181.
M. Muttenthaler, F. Albericio and P.E. Dawson, Nat. Protoc., 2015,
1
5
10(7), 1067.
4
| J. Name., 2012, 00, 1-3
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